The AAPS Journal, Vol. 13, No.

4, December 2011 (# 2011)

DOI: 10.1208/s12248-011-9290-9

Research Article
BDDCS Applied to Over 900 Drugs
Leslie Z. Benet,1,6 Fabio Broccatelli,1,2 and Tudor I. Oprea3,4,5

Received 17 May 2011; accepted 22 June 2011; published online 5 August 2011
Abstract. Here, we compile the Biopharmaceutics Drug Disposition Classication System (BDDCS)
classication for 927 drugs, which include 30 active metabolites. Of the 897 parent drugs, 78.8% (707) are
administered orally. Where the lowest measured solubility is found, this value is reported for 72.7% (513)
of these orally administered drugs and a dose number is recorded. The measured values are reported for
percent excreted unchanged in urine, LogP, and LogD7.4 when available. For all 927 compounds, the in
silico parameters for predicted Log solubility in water, calculated LogP, polar surface area, and the
number of hydrogen bond acceptors and hydrogen bond donors for the active moiety are also provided,
thereby allowing comparison analyses for both in silico and experimentally measured values. We discuss
the potential use of BDDCS to estimate the disposition characteristics of novel chemicals (new molecular
entities) in the early stages of drug discovery and development. Transporter effects in the intestine and
the liver are not clinically relevant for BDDCS class 1 drugs, but potentially can have a high impact for
class 2 (efux in the gut, and efux and uptake in the liver) and class 3 (uptake and efux in both gut and
liver) drugs. A combination of high dose and low solubility is likely to cause BDDCS class 4 to be
underpopulated in terms of approved drugs (N=53 compared with over 200 each in classes 13). The
inuence of several measured and in silico parameters in the process of BDDCS category assignment is
discussed in detail.
KEY WORDS: BDDCS; biowaiver; dose number; extent of metabolism; permeability rate.

In 2005, Wu and Benet (1) introduced the Biopharmaceutics

Drug Disposition Classication System (BDDCS). Wu and
Benet recognized that there was a very strong correlation
between the intestinal permeability rate and the extent of
metabolism. For example, Benet et al. (2) noted that for the
29 drugs and endogenous substances for which human jejunal
permeability rate measurements were available, there was an
excellent correlation between these permeability rate measurements and the extent of drug metabolism in humans.
Fourteen of the 16 drugs exhibiting human intestinal permeability rates greater than metoprolol were extensively metabElectronic supplementary material The online version of this article
(doi:10.1208/s12248-011-9290-9) contains supplementary material,
which is available to authorized users.
1

Department of Bioengineering & Therapeutic Sciences, Schools of

Pharmacy and Medicine, University of California San Francisco, 533
Parnassus Avenue, Room U-68, San Francisco, California 941430912, USA.
2
Laboratory of Chemometrics, Department of Chemistry, University
of Perugia, Via Elce di Sotto, 10, 60123 Perugia, Italy.
3
Sunset Molecular Discovery LLC, 1704 B Llano Street, Suite 324,
Santa Fe, New Mexico 87505, USA.
4
Department of Biochemistry and Molecular Biology, Division of
Biocomputing, University of New Mexico School of Medicine, Mail
stop code 116145( Albuquerque, New Mexico 87131, USA.
5
Center for Biological Sequence Analysis, Technical University of
Denmark, Kemitorvet, Building 208, Lyngby 2800, Denmark.
6
To whom correspondence should be addressed. (e-mail: leslie.
benet@ucsf.edu)

olized, while 11 of 12 drugs showing permeability rates less

than metoprolol were poorly metabolized. Two drugs showing disparity between the permeability rate and metabolism,
cephalexin and losartan, exhibit permeability rates that differ
by no more than 16% from metoprolol (2). Since the
coefcients of variation for the human permeability parameters range from 29% to 130%, these borderline compounds
may in fact also have followed the correlation. The correlation between the extent of metabolism and human intestinal
jejunal permeability was markedly better than that observed
for intestinal jejunal permeability and partition coefcient by
Takagi et al. (3), who noted that Log P measured and
calculated correctly predict high versus low permeability only
about two thirds of the time. Wu and Benet (1) reasoned that
it might be easier to utilize metabolism in assigning drug
classication since it is difcult and expensive to determine
human intestinal permeabilities and since it is also difcult to
obtain quantitative mass balance measures that show 90%
absorption, the FDA criterion for a biowaiver as dened in
the FDA BCS Guidance (4), based on the work of Amidon
et al. (5). Therefore, in proposing the BDDCS classication
system, Wu and Benet (1) substituted extensive and poor
metabolism for high and low permeability in the BCS while
utilizing the same criteria as the FDA for high and low
solubility. That is, a high solubility compound at the highest
marketed dose strength would be soluble in 250 mL of water
over the pH range of 17.5 at 37C. Using the BDDCS, Wu
and Benet (1) classied 168 drugs based on the extent of
metabolism and solubility.

519

1550-7416/11/0400-0519/0 # 2011 American Association of Pharmaceutical Scientists

520
BDDCS VERSUS BCS
Although BDDCS grew out of the FDAs BCS Guidance
(4), Wu and Benet (1) proposed BDDCS as a means to
predict the drug disposition characteristics of novel chemicals
(here, referred to as new molecular entities, NMEs) during
the early stages of drug discovery and development. Such
examples will be discussed below. Recently, Benet and
Larregieu (6) reviewed the differences between BCS and
BDDCS in terms of purpose and basis. The purpose of BCS is
to facilitate biowaivers of in vivo bioequivalence studies for
drugs that exhibit no signicant intestinal absorption
problems. In contrast, the purpose of BDDCS is to predict
the drug disposition of NMEs as well as potential drug
drug interactions for NMEs and drugs on the market with
respect to the intestine and liver. Very recently, a consensus
paper with respect to BCS, BDDCS, and regulatory
guidances has been published (7).
Both BCS and BDDCS use the same criteria for
solubility. Therefore, there is no difference in the basis
between the two systems with respect to this parameter. As
noted above, BDDCS predictions and classication are based
on the intestinal permeability rate, not the extent of permeability. There is some ambiguity with respect to the basis for
BCS, as reviewed by Benet and Larregieu (6). The initial
permeability studies of Amidon, Lennerns, and colleagues
(5,8), as summarized by Takagi et al. (3), show a good
correlation between human intestinal permeability rate and
the extent of absorption, as detailed earlier in the rst
paragraph of this paper. However, the criterion listed in the
FDA BCS Guidance (4) is a drug substance is considered
to be highly permeable when the extent of absorption in
humans is determined to be 90% or more of an administered
dose based on a mass balance determination or in comparison
to an intravenous reference dose [emphasis added by the
FDA]. Although permeability rate methods are listed in the
FDA BCS Guidance (4), we are unaware of any drug that has
been certied by the FDA as class 1 eligible for in vivo
biowaiver where there is no conrmatory 90% absorption
data. This ambiguity does not exist in the Guideline on the
Investigation of Bioequivalence issued in 2010 by the
European Medicines Agency (EMA), which only allows
in vivo biowaivers based on the extent of absorption (9).
This difference in the permeability basis between BCS and
BDDCS is brought home in a recent publication by FDA
scientists (10). Chen and Yu (10) note that the FDA has
classied as highly permeable a number of drugs where
absorption is 90% in humans, but the measured permeability rates of these compounds are less than that for
metoprolol (cefadroxil, cephradine, levooxacin, loracarbef,
ooxacin, and sotalol), and in one case (pregabalin), the
measured permeability rate is less than that for mannitol. As
previously recognized (3), BCS is inuenced by transporter
effects. For example, large amino acid transporter-1 (LAT-1)
is expressed in Caco-2 cells (11), and pregabalin is a LAT-1
substrate as noted in the package insert (12), which may
explain this discrepancy. Since pregabalin is a zwitterion, its
high oral bioavailability (90%) may be attributed to LAT-1
transport, an effect that is not taken into account by BCS.
Thus, although in general drugs exhibiting high intestinal
permeability rates show a high extent of absorption and a

Benet, Broccatelli and Oprea

high extent of metabolism in both BCS and BDDCS, there
are a number of drugs that could be classied as highly
permeable in the BCS system based on absorption 90% but
would be predicted to be poorly metabolized based on the
low intestinal permeability rate, the basis for BDDCS
classication. By evaluating metabolism, not permeability,
BDDCS is not subject to variability due to transporter effects.
In general, classication of drugs between BCS and
BDDCS only differ about 510%. However, for class 1 drugs
where FDA has granted biowaivers, we estimate that the
difference between BCS and BDDCS occurs for about 40%
of drugs. We cannot make a more accurate estimate since the
listing of all drugs granted biowaivers by the FDA is
condential. The percentage difference is high due to the
ease in determining whether a drug is >90% absorbed (class 1
in BCS) when a drug is almost completely eliminated
unchanged in the urine (class 3 in BDDCS).
BDDCS AND ITS USE
In 1995, Wu and Benet (1) reviewed 131 drugs that had
been classied into the four BCS categories in the literature
through the end of 1994. Ten of these drugs had been listed in
different classes by different authors. Wu and Benet (1)
recognized that the major route of elimination in humans for
the great majority of high-permeability class 1 and class 2
drugs was metabolism, while the major route of elimination
for the poorly permeable class 3 and class 4 drugs in humans
was renal and biliary excretion of unchanged drug. They also
noted that the major route of elimination via cytochrome
P450 3A4 (CYP3A4) was only observed for the class 1 and
class 2 drugs and that for the class 3 and class 4 drugs
CYP3A4 was not a major contributor to elimination for any.
Since the extent of metabolism is better characterized than
the extent of absorption, for marketed drugs, Wu and Benet
proposed that in BDDCS, drugs be categorized in terms of
the extent of metabolism and solubility versus permeability
rate and solubility (1). This immediately eliminated the
situation where drugs were classied in more than one class
because of the uncertainty of permeability measures from
study to study. The implication from the BDDCS for an NME
is that if a surrogate measure of intestinal absorption rate is
available, such as permeability rate through a Caco-2 cellular
system, it would be possible to predict the major route of
elimination for this new molecular entity in humans prior to
its in vivo dosing to either animals or humans. Work is
ongoing in our laboratory to determine the degree of
accuracy in predicting BDDCS class for an NME based only
on in vitro permeability measures prior to studies determining
the extent of metabolism. Thus, Benet and Wu (1) proposed
the BDDCS as shown in Fig. 1 with 70% metabolism being
the cutoff for extensive metabolism. They also noted that there
were relatively few drugs where the extent of metabolism was
between 30% and 70% and that most drugs are either very
highly metabolized or very poorly metabolized.
Figure 2 summarizes the predictions from BDDCS
related to the effects of enzymes and transporters in the gut
and liver following oral dosing of drugs (1,13). For class 1,
highly solublehigh permeability rateextensively metabolized drugs, transporter effects in the intestine and the liver
have no clinical impact. Even compounds like verapamil,

BDDCS Applied to Over 900 Drugs

Fig. 1. The Biopharmaceutics Drug Disposition Classication System

(BDDCS) as proposed by Wu and Benet (1)

which can be shown in certain cellular systems (e.g., MDR1MDCK) to be a substrate for P-glycoprotein (P-gp), exhibit
no clinically signicant P-gp substrate effects in the gut and
the liver. Thus, a major proposition of BDDCS is that
although class 1 drugs may be shown in cellular systems to
be substrates for transporters found in the intestine and the
liver, this has no clinical relevance. However, a caution is in
order here. At this time, BDDCS predictions only apply to
the intestine and the liver since class 1 drugs could be
substrates for transporters at the bloodbrain barrier and in
the kidney.
From Fig. 2, it can be seen that for class 2 drugs, efux
transporter effects will predominate in the intestines. Thus,
transporterenzyme interplay will be primarily important for
class 2 compounds that are substrates for CYP3A and phase
II gut enzymes (e.g., glucuronosyltransferases, sulfotransferases), where efux transporter effects can control the
access of the drug to the gut enzymes. BDDCS predicts that
both uptake and efux transporters can affect class 2 drug
disposition in the liver. Thus, inhibition or induction of uptake
hepatic transporters such as the SLCOs (OATPs) and the
SLC22As (OATs and OCTs) as well as the drug efux hepatic
transporters ABCB1 (P-gp), ABCG2 (BCRP), and ABCCs
(MRPs) can lead to changes in hepatic metabolism even when
hepatic enzymes are unaffected.
BDDCS predicts that for class 3, highly solublepoor
permeability ratepoorly metabolized drugs, uptake transporters will be important for intestinal absorption and liver
entry for these poorly permeable compounds (Fig. 2). However, once these drugs get into the enterocyte or the

521
hepatocyte, efux transporter effects can also occur. Similarly,
uptake and efux transporter effects would be expected for
the poorly soluble class 4 compounds. Because they are
numerically underrepresented, one might expect that class 4
drugs are more difcult to manage therapeutically, i.e., there
are transporter effects just as in class 2, except these drugs are
not signicantly metabolized. As will be shown subsequently,
plotting the maximum recommended therapeutic daily dose
(14) versus BDDCS and looking at the actives (low dose)
versus inactives (high dose, safer) revealed no such
relationship. It is more likely that fewer drugs are represented
in class 4 because of the combined negative characteristics of
high dose and (comparatively) low solubility, which leads to
high variability. Since the FDA criteria for solubility is
measured in water, we suspect that the approved class 4
drugs have adequate solubility in the natural surfactant
containing intestinal uids.
Details and explications for the predictions in Fig. 2 have
been presented in recent reviews from the Benet lab (13,15,16).
However, in large part, the predictions in Fig. 2 were based on
clinical and experimental observations. That is, we are unaware
of any clinically signicant effects of the uptake and efux
transporters in the gut and liver on class 1 drugs, even when such
drugs have been shown in cellular systems or other organs
besides the gut and the liver to be substrates of the uptake and
efux transporters. These effects, however, might become
relevant in overdosage situations, e.g., when combined with
strong inhibitors of their respective metabolizing enzyme, when
liver failure is manifest, or when accidentally overdosed.
Similarly, we are unaware of the clinically signicant effects of
the uptake transporters in the gut for class 2 drugs even when
these drugs are shown to be substrates of uptake transporters in
the liver.
BDDCS also allows potential drugdrug interactions to
be predicted (16,17). For class 1 drugs, only metabolic
interactions need to be considered in the intestine and the
liver. For class 2 drugs, metabolic, efux transporter, and
efux transporterenzyme interplay in the intestine must be
taken into consideration, while in the liver, metabolic, uptake
transporter, efux transporter, and transporterenzyme interplay (both uptake and efux) can occur. For class 3 and class 4
drugs, uptake transporter, efux transporter, and uptakeefux
transporter interplay will be of major importance.
BDDCS classication may also be useful in predicting
the effect of high-fat meals on the extent of bioavailability (F)
for an NME. In general, F for class 1 drugs is unaffected by
high-fat meals; F is generally increased for class 2 drugs and
generally decreased for class 3 drugs (18). Custodio et al. (19)
have observed that these ndings would be the outcomes
expected if a component of high-fat meals inhibited both the
uptake and efux transporters. However, even if this were
true, high-fat meals would be expected to have many other
effects than inhibiting transporters. We estimate that the
predicted effect of high-fat meals on F is only correct about
70% of the time.
CAUTION

Fig. 2. Transporter effects predicted by BDDCS following oral dosing

It is surprising that such a simple four-category process

as indicated in Fig. 2 works so well in predicting drug
disposition, transporterenzyme effects, and drug interac-

522
tions. It is obvious, however, that this simple four-category
system will not predict every interaction. BDDCS does not
propose that every drug in the class will be substrates or not
substrates for the uptake and efux transporters. Rather,
BDDCS helps prioritize what interactions should and should
not be investigated. For example, the class 2 drug felodipine
has been shown not to be affected by the intestinal or hepatic
efux transporters (20). Recently, our laboratory has shown
the importance in humans of hepatic uptake transporters for
the drugs atorvastatin and glyburide (21,22). These interactions were predicted based on cellular, isolated organ, and
animal studies (2224). Even when such preliminary studies
conrm BDDCS predictions, this may not always be the case.
Warfarin is a class 2 drug and, thus according to BDDCS, may
be a substrate for a hepatic uptake transporter. In vitro
studies in human and rat hepatocytes showed that rifampin
would decrease warfarin metabolism by 30% (25), a similar
extent to that found for our in vitro results with glyburide
(22). However, our recently published study examining the
effects of a single dose of rifampin on the pharmacokinetics of
warfarin in healthy volunteers showed that OATP uptake in
vivo in humans was not clinically signicant for warfarin (25).
Similarly, although warfarin appears to be both a substrate
and inhibitor of liver-bound P-gp (26), this has not been
regarded as clinically signicant; one P-gp haplotype, however, is clearly associated with low-dose warfarin in a 201
patient sample (27). This emphasizes again the caution that
BDDCS only predicts with respect to transporters what might
occur, but not that the effect will always occur. Furthermore,
our example above (25) reinforces the well-recognized
concept that observations in cellular systems and animal
models must be tested in vivo in humans before the
signicance of the effect is assumed.
WHY DID WE PREPARE THIS PAPER?
Wu and Benet (1) recognized that the FDAs BCS
approach (4) held the potential for predicting the drug
disposition characteristics and drug interactions for NMEs
as well as for drugs on the market. The use of BDDCS in the
area of systems chemical biology (28) has been previously
outlined (29), and computational models to assign BDDCS
class from molecular structure have been proposed (30).
However, to test the usefulness of BDDCS, to examine
patterns within the BDDCS classes and among them, and to
gain further perspectives, it is necessary to compile a large
database, at least with respect to drugs that have reached the
market. Since BDDCS makes predictions related to hepatic
elimination in addition to intestinal absorption, such a database should include as many drugs as possible where systemic
concentrations are relevant. Thus, approximately one quarter
of the drugs categorized here are administered exclusively by
non-oral routes. We also felt strongly that the information
provided in the database should be based, where available,
not only on the in silico predictions of those parameters but
also on experimental values. We noted that many of the
solubility values used in BCS analyses are frequently in silico
predictions of solubility. For example, in the often quoted
paper of Willmann et al. (31) describing a physiological model
for the estimation of the fraction dose absorbed in humans,
the measured solubility values were only included for only 22

Benet, Broccatelli and Oprea

of the 126 drugs evaluated. The solubility for the great
majority of the drugs utilized in the Willmann et al. (31)
analysis came from the compilation of Zhao et al. (32). These
latter workers evaluated human intestinal absorption data for
241 drugs (32). Of the 241 drugs, Zhao et al. compared the
experimental results for 26 of the compounds with the
predicted solubility utilizing the method of Meylen et al.
(33) based on octanol water partition coefcients. For these
26 drugs, the measured versus calculated solubility differs by a
factor of 5.76.0-fold, the greatest difference being 23-fold.
Thus, at present, in silico methodologies for aqueous solubility prediction are not sufciently accurate for the BDDCS
analysis not only due to the inherent limitations of such
methods but also to its denition, i.e., BDDCS solubility
categorization depends on the maximum strength dose and
the effect of pH. Experimental solubility values were included
in this compilation wherever they could be found in the
literature (577 drugs). Qualitative evaluations such as practically insoluble in water, which relate to upper limits, and
highly soluble in water were used in the absence of
published solubility values from a reliable source and were
the basis of the BDDCS assignment when no measured value
is listed in the table.
Frequently, large compilations such as the ones presented here are carried out with the assistance of graduate
students, postdoctoral fellows, and auxiliary personnel. In our
experience, this can lead to unevenness in the quality of the
data presented in the table. For each of the drugs listed here,
decisions concerning the experimental values to be listed and
classication assigned were made during the multiple joint
meetings of Drs. Benet and Oprea between February 2007
and February 2011. Then, Dr. Broccatelli captured potential
errors by cross-checking many references. Therefore, if there
are errors in the parameters or in the assignments, this can
only be attributable to the authors.
MEASURED PARAMETERS (IN ORDER
OF DIFFICULTY)
Solubility
There are a number of issues concerning the choice of
the high versus low solubility criteria and which representative experimental values should be listed. The high solubility
criterion that the highest dose strength on the market is
soluble in 250 mL or less of water over the pH range 17.5 at
37C was an arbitrary decision made by Amidon et al. (5) and
incorporated into the regulatory Guidances (4,9). Wu and
Benet (1) found that this cutoff criterion in BCS appeared to
work well for BDDCS, and thus, we have continued to use
this arbitrary, discriminatory criterion. The FDA criteria (4)
require the solubility measurements to be made in water, not
simulated intestinal uid containing a surfactant, and the
solubility values listed in the table are values in water.
Furthermore, the FDA criteria evaluate the cutoff between
high and low solubility using the value for the lowest
solubility over the pH range 17.5 (realistically measured at
pH 1.2, 4.5, and 6.8 as indicated in the FDA Guidance).
Furthermore, the solubility is to be measured at 37C. The
values in Tables I, II, III, IV, and V are the authors best
recommendation based on experimental literature data for

Abacavir sulfate
Acarbose
Acebutolol hydrochloride
Acetaminophen; paracetamol
Acetohexamide
Acetylsalicylic acid; aspirin
Adenosine
Alfacalcidol
Alfentanil
Alfuzosin
Aliskiren
Alosetron
Alprazolam
Alprenolol
Ambrisentan
Ambroxol
Amifostine
Aminophenazone; aminopyrine
Amitriptyline hydrochloride
Amlodipine
Amoxapine
Amsacrine
Anastrozole
Anhydrovinblastine;
anhydrovincaleukoblastine
Antipyrine; phenazone
Apomorphine
Asenapine
Atomoxetine
Azathioprine
Bambuterol
Benazepril
Bendamustine
Benidipine
Benserazide
Benznidazole
Bepridil
Beraprost
Betamethasone
Betaxolol
Bimatoprost
Biperiden
Bopindolol
Bortezomib
Brimonidine
Bromazepam
Bromocriptine
Bromperidol
Budesonide
Buomedil hydrochloride
Bupivacaine
Buprenorphine hydrochloride
Bupropion
Busulfan (busulphan)

Generic name

mg
mg
mg
mg
mg
mg
mg/mL
g
mg/mL
mg
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg
mg
mg/mL
mg
mg/mL

mg
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg/mL
mg/mL
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg

500
2.56
10
60
100
20
40
5
8
50
100
400
0.04
5
20
0.30
2
2
1
2
6
5
10
3
300
5
8
100
2

Maximum
strength
dose unit

300
100
400
1000
500
500
3
1
0.5
10
300
1
2
200
10
30
5
300
150
10
150
33.33
1
1

Maximum
strength
dose value

Tablets
Tablets
Tablets
Capsules
Tablets
Tablets
Tablets
Solution
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Solution
Tablets
Tablets
Solution
Solution
Tablets
Capsules
Tablets
Capsules
Tablets
Solution
Tablets
Tablets
Tablets

Tablets
Tablets
Capsules
Tablets
Tablets
Tablets
Solution
Capsules
Solution
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Solution
Tablets
Tablets
Tablets
Tablets
Solution
Tablets
Solution

Formulation

(i.v.)

(i.v.)

(i.v.)

(i.v.)

(i.v.)

Oral
Injection (s.c.)
Oral
Oral
Oral
Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Ophthalmic
Oral
Oral
Injection (i.v.)
Ophthalmic
Oral
Oral
Oral
Oral
Oral
Injection (epidural)
Oral
Oral
Oral

Oral
Oral
Oral
Oral
Oral
Oral
Injection
Oral
Injection
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Injection
Oral
Oral
Oral
Oral
Injection
Oral
Injection

Route

1.0
0.3
0.000008
0.3
0.2

0.4
5
19
0.066
0.451
0.8
1
3.3
3.3
1.5
0.17
0.8
0.09
0.02
0.17
17
312
0.1

0.02

1.9

0.002
0.001
0.08

0.1
0.03
0.4
0.6

0.008
0.002

0.009
0.04
0.002
0.002

0.001
0.0005

0.008
0.0004

0.02
0.0006

27.8
10
33
78

1700
20

0.5
10

55.55
1000

0.003
0.00007
0.1
0.02
0.7
0.01

0.2
0.6
0.2

23.7
3.43
10
5

350
61
0.073
50
0.06
10.9

0.02

Dose
number

77

Measured
solubility
(mg/mL)

2
0.5
0
23.6
2
1
0.5
1

10

4.8
15

0.5

0.5
0.3
1
1.5
1
0
0.5
1
1
1

10
10
0.5

1
10

1.4
0
8
0.5
11
25
6
20
0.5
5
8
0.69

1.2
1
10
3

% Excreted
unchanged
in urine

188.23
267.33
285.78
255.36
277.27
367.45
424.50
358.27
535.65
257.25
260.25
366.55
398.50
392.47
307.44
415.58
311.47
380.49
384.25
292.14
316.16
654.61
420.33
430.55
307.39
288.44
467.65
239.75
246.30

286.34
645.62
336.43
151.17
324.40
180.16
267.25
400.65
416.53
389.46
551.77
294.36
308.77
249.36
376.46
364.08
214.22
231.30
277.41
408.89
313.79
393.47
293.37
792.98

MW drug

3.23
1.47
0.11
3.39

2.81
1.87
1.32
3.77
2.83
2.72
2.49
2.06
2.07
2.29
3.27
2.91
3.67
4.33

2.45

0.96
1.44
1.05
0.74

0.96
1.13

2.77
1.90

0.62
0.50

0.20
0.68
3.63
0.70
3.80
1.52

0.52

3.41
4.98

2.74
3.20

0.78
2.05

4.25

1.94
2.81

0.10
1.50

2.30

3.70

4.92
3.00

3.27
0.52

1.54
4.59
3.34
2.70
0.75

4.22

1.94
0.55

2.00

0.02
2.58
1.10

0.28

3.69

1.00
2.95
1.68

1.26
1.34

2.12
3.10

1.04

2.10
1.18
2.45

0.19
0.40
0.36
2.57
1.10

1.20

Measured
LogD74

2.16

1.20
8.83
1.71
0.20
2.44
1.19
0.98

0.57

0.80
1.98
1.26
1.73

Measured
LogP

Measured
LogS molar

Table I. Measured and In Silico Data for 351 BDDCS Class 1 Drugs

0.81
6.66
1.71
0.49
2.25
1.02
2.16
8.24
2.13
2.55
3.51
1.74
2.56
2.65
3.33
2.66
1.85
1.04
4.85
3.43
3.41
4.69
1.29
6.11
0.20
2.49
4.58
3.94
0.51
0.56
1.82
2.76
7.41
2.90
0.90
6.20
2.04
1.79
2.32
1.75
4.94
4.98
0.78
1.49
1.70
6.58
4.00
2.91
2.93
3.69
3.99
3.21
0.59

1.79
2.73
2.41
1.14
2.72
1.56
1.84
0.83
5.69
2.13
2.65
4.29
4.64
3.61
1.66
5.44
1.93
3.92
4.09
2.00
3.47
6.80
3.84
4.71
1.23
3.53
3.58
1.99
1.20

CLogP

3.07
3.30
1.46
1.66
3.13
0.94
1.37
5.86
4.12
3.80
3.09
3.26
3.68
0.86
3.35
2.44
3.12
2.23
2.29
1.79
2.43
1.37
3.60
7.12

minVSLgS
37.5

2
3
1
2
6
4
5
4
0
7
4
3
5
5
4
4
2
3
6
5
3
6
3
6
5
2
5
2
4

6
19
5
2
4
3
8
2
6
8
7
2
3
3
5
3
5
3
1
5
3
5
4
8

HBA

0
2
0
1
1
2
2
1
0
7
1
0
3
3
2
4
1
2
4
2
1
3
1
2
0
1
2
1
0

3
14
3
2
2
1
4
2
0
2
4
1
0
2
1
3
4
0
0
2
1
2
0
2

HBD

22.02
46.92
10.59
23.68
99.66
94.24
101.61
69.78
112.85
169.84
87.81
10.84
95.05
104.22
55.03
100.52
23.73
64.71
151.53
58.94
52.40
118.24
42.01
99.25
46.76
33.72
64.50
32.84
92.04

95.80
351.80
97.05
55.41
103.22
68.21
135.44
45.12
77.73
108.88
156.62
44.23
33.27
46.24
70.11
64.50
106.66
26.79
1.18
105.47
34.47
85.11
61.36
130.05

PSA

BDDCS Applied to Over 900 Drugs

523

mg
Active metabolite
mg
mg
mg
mg
mg/mL
mg
mg
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg
mg
Active metabolite
mg
mg

6.48
2000
0.8
3
30
500
2
250
25
192
4
200
5
1
2
300

10

Butabarbital
Butalbital
Butorphanol
Caffeine
Capecitabine
Caprylidene
Carbidopa
Carmustine

Caspofungin acetate
Cefoperazone
Cerivastatin
Cetrorelix
Cevimeline
Chloral hydrate
Chlorambucil
Chloramphenicol
Chlordiazepoxide
Chlormethiazole; clomethiazole
Chlorpheniramine
Chlorpromazine
Cilazapril
Cisplatin
Clemastine
Clindamycin hydrochloride
hydrate
Clobazam
Clobric acid
Clomiphene citrate
Clomipramine
Clonazepam
Clorazepate
Cocaine
Codeine monohydrate
Colchicine
Cortisone
Cyanocobalamin (vitamin B12)
Cyclizine
Cyclobenzaprine
Cyclophosphamide
Cyproheptadine
Cytarabine
Dabigatran etexilate
Dantrolene
Darifenacin
Debrisoquine
Desalkylurazepam
Desipramine
Desmethyldiazepam
(nordazepam)
Desogestrel
Dexamethasone
Dexmethylphenidate

1.5
0.75
10

200
10

50
75
2
15
0.1
60
0.6
25
5
50
10
50
4
20
110
100
15
20

mg/mL
mg
mg
mg/mL
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg

100
50
5
65
500
20000
25
7.70

Generic name

mg
mg
mg

mg
mg
mg
mg
mg
mg
mg
mg

Maximum Maximum
strength
strength
dose value dose unit

Tablets
Tablets
Tablets

Tablets
Tablets

Tablets
Tablets
Tablets
Tablets
Solution
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Solution
Capsules
Capsules
Tablets
Tablets

Tablets

Solution
Powder
Tablets
Solution
Capsules
Capsules
Tablets
Capsules
Capsules
Capsules
Tablets
Tablets
Tablets
Solution
Tablets
Capsules

Tablets
Tablets
Tablets
Caplets
Tablets
Powder
Tablets
Implant

Formulation

Oral
Oral
Oral

Oral
Oral

Oral
Oral
Oral
Oral
Topical (nasal)
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral

Oral

Oral
Oral
Oral
Oral
Oral
Oral
Oral
Topical (skin,
membranes)
Injection (i.v.)
Injection (i.v.)
Oral
Injection (s.c.)
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Injection (i.v.)
Oral
Oral

Route

0.32
0.092

0.057

29

1.8
2

0.02
0.03

0.7

0.003

0.2
0.2

0.0006
0.00005
0.4
0.002
0.02
0.0002
0.005
0.004

0.08

0.1
1.6
435
45
0.28
12.5
8.7
200
40
3.636

0.2

0.2

0.188
45
1.11

0.003
0.03

0.002
0.02

0.0002
0.0007
0.4
0.05
0.08

8300
12
2.5
2
10
400
1
2.53
2.3
40

0.00002

0.04
0.008

2.5
3.8

195
8

0.01
0.01
0.08

Dose
number

2
21.5
26

Measured
solubility
(mg/mL)

0
2.6
0.5

0.5
0.5
0.5
6.5
0.5
11
0
5
12.5
12
0.5
2
0.5

0.5
0.5
1
0.1

5.7
8

0.5
5
0.5
0.05
10
0.5
0
2.3
5
13

1.4
29
24
3
13.5

1
3.6
2
1
3
0
5.3
0.5

% Excreted
unchanged
in urine

Table I. (Continued)

310.48
392.47
233.31

300.75
214.65
405.97
314.86
315.72
314.73
303.36
299.37
399.45
360.45
1355.40
266.39
275.40
261.09
287.41
243.22
627.75
314.26
426.56
175.24
288.71
266.39
270.72

1093.34
645.68
459.56
1431.07
199.32
165.40
304.22
323.13
299.76
161.65
274.80
318.87
417.51
300.06
343.90
424.99

212.25
224.26
327.47
194.19
359.36
470.70
226.23
214.05

MW drug

2.99
3.63

3.68

0.78

2.54
2.20

1.94
1.80

0.75
2.70
4.90
2.93

0.63
4.69
2.51
3.80
1.70

2.30
1.19
1.30
1.47

2.28
0.14
0.95
3.11
2.04
1.49
0.14
0.81
1.90

3.50

2.12
2.57
6.70
5.19
2.41

2.53
5.49
2.16

0.99
3.25
1.14
2.44
2.12
3.38
5.41

0.74

1.53

2.26
0.07

1.65

Measured
LogP

3.20
0.68
2.73

0.10
2.62
2.07
2.17
1.08

1.70
1.40
2.11
2.18
1.21

0.37
2.25

1.96
1.75

2.21
0.96
1.14

Measured
LogS molar

1.83
0.28

2.96
2.78
1.40
2.93

0.77

2.24

0.63

2.76
2.41
1.13
2.30
0.21
1.03
1.47

1.90
1.13

3.04

1.61
1.59
1.00
2.19
2.12
1.38
2.82
2.25

2.12

1.53

0.07

1.45

Measured
LogD74

4.86
3.65
1.61

3.63
1.63
4.24
2.56
3.96
2.36
2.85
1.40
3.90
3.52
0.05
2.97
2.58
1.92
3.19
0.60
7.74
3.44
3.74
2.59
3.78
0.80
3.69

5.68
1.79
2.56

2.44
2.82
7.15
5.92
2.38
2.51
2.57
0.98
1.20
1.30
1.36
3.80
5.10
0.80
5.30
2.20
4.13
1.63
3.62
0.90
2.81
4.47
3.02

2.95
0.22
3.56
0.40
1.14
0.72
3.63
1.28
3.79
1.68
3.15
5.30
1.47
1.68
5.45
2.57

3.18
3.47
2.00
7.00
1.32
0.77
0.27
2.79
2.65
1.80
1.57
2.69
0.78
2.56
2.99

1.58
1.63
3.73
0.04
0.84
9.97
0.45
1.32

CLogP

2.42
2.74
2.40
1.95
3.45
7.69
1.33
2.50

minVSLgS
37.5

1
5
2

2
3
2
2
4
4
3
4
6
5
17
2
1
2
1
7
8
5
3
3
2
2
2

18
11
6
18
2
2
3
5
3
1
2
2
6
0
2
6

3
3
3
3
6
3
6
2

HBA

1
3
1

0
1
0
0
1
2
0
1
1
2
9
0
0
1
0
4
2
1
1
2
1
1
1

16
4
3
17
0
2
1
3
1
0
0
0
2
2
0
4

2
2
2
0
3
0
5
1

HBD

22.56
104.22
41.64

37.99
49.94
10.28
1.75
86.30
82.98
55.30
41.94
87.54
99.93
492.69
2.35
1.18
44.31
1.18
133.23
146.19
118.74
56.52
52.16
42.15
15.14
42.15

454.42
227.75
104.98
543.33
9.97
45.12
41.70
122.11
45.94
10.24
11.42
1.75
106.36
75.29
9.97
110.49

83.96
83.96
46.61
48.50
124.33
81.19
132.39
69.78

PSA

524
Benet, Broccatelli and Oprea

Everolimus
Exenatide
Famciclovir
Fentanyl
Fesoterodine
Finasteride
Fludarabine
Fludarabine
5-monophosphate
Fludrocortisone acetate
Flumazenil
Flunitrazepam
Fluorouracil
Fluoxetine
Flurazepam
Fluvastatin sodium
Fluvoxamine
Formoterol fumarate
Fosuconazole
Frovatriptan
Galantamine
Gemcitabine hydrochloride
Glibornuride
Goserelin
Granisetron
Guanabenz
Heparin; enoxaparin

Dextromethorphan
hydrobromide
Dezocine
Diazepam
Diclofenac
Dihydroquinidine;
hydroquinidine
Dilevalol
Diltiazem
Diphenhydramine
Dobutamine hydrochloride
Dolasetron
Dosulepin; dothiepin
Doxazosin
Doxepin
Doxorubicin
Duloxetine hydrochloride
Eletriptan hydrobromide
Enalapril
Enfuvirtide
Epirubicin
Ergonovine; ergometrine
Ergotamine tartrate
Escitalopram
Esmolol
Esomeprazole magnesium
Estradiol
Eszopiclone
Ethanol
Ethinylestradiol
Ethosuximide
Etonogestrel

mg
mg/mL
mg
mg/mL
mg
mg
mg
mg
g/inhalation
mg
mg
mg
mg/mL
mg
mg
mg
mg
mg/mL

10

0.1
0.1
1
25
20
30
40
100
12
100
2.5
12
40
25
10.8
1
16
20

mg
mg
mg
mg/mL
mg
mg
mg
mg
mg/mL
mg
mg
mg
mg/mL
mg/mL
mg
mg
mg
mg/mL
mg
mg
mg
mg/mL
mg
mg
g

50
120
50
12.5
100
75
8
100
2
67.3
40
20
90
2
0.2
2
20
10
20
2
3
62
1
250
157

mg
mg/mL
mg
mg
mg
mg
Active metabolite
mg

mg/mL
mg
mg
mg

15
10
50
300

1
0.25
500
1.6
8
5

mg

60

Tablets
Solution
Tablets
Solution
Capsules
Capsules
Capsules
Tablets
Powder
Tablets
Tablets
Tablets
Solution
Tablets
Implant
Tablets
Tablets
Solution
(10,000 units/mL)

Tablets

Tablets
Capsules
Capsules
Solution
Tablets
Tablets
Tablets
Capsules
Solution
Capsules
Tablets
Tablets
Solution
Solution
Tablets
Tablets
Tablets
Solution
Tablets
Tablets
Tablets
Solution
Tablets
Capsules
Tablets (and 68 mg
implant s.c)
Tablets
Solution
Tablets
Lozenge
Tablets
Tablets

Solution
Tablets
Tablets
Tablets

Tablets

Oral
Injection (i.v.)
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Topical (aerosol)
Oral
Oral
Oral
Injection (i.v.)
Oral
Injection (s.c.)
Oral
Oral
Injection (i.v.)

Oral

Oral
Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Injection (i.m.)
Injection (i.v.)
Oral
Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Oral
Oral
Topical (skin.
membranes)
Oral
Injection (s.c.)
Oral
Oral
Oral
Oral

Injection (i.v.)
Oral
Oral
Oral

Oral

0.03
0.001

39.2
0.51

100
11
50

10
15
0.2

0.14
0.128
0.004
12.2
15.2
500
50
14.869
0.66

3.53

0.00004
0.006

0.5

0.005

0.005
0.0002
0.003
0.03
0.00007

1.0

0.003

0.01

0.008
0.0003
0.0001
0.5

0.4

0.2
0.09

20
0.5
0.09

0.01
25
250
25
256
0.043

0.00008
0.004

0.04
0.003

0.0002

0.7
0.02
0.1

0.02

10
2

4
25
1000

10

500

1000

16

20
0.057
9
11.1

15

0.5

6
20
8
0.5
20
11

1
0.5
0.5
5
1.25
0.1
1.5
2
8

0
8
0
0.5
24

8
0.5
0.5
0.5
5
2.5
3
25
0.1

0
3.5
0
5
10
0
9.5

2.5
2
2
0.1
0
5

1
0.5
0.5
18

0.19

422.50
303.30
313.29
130.08
309.33
387.89
411.48
318.34
344.41
386.26
243.31
287.36
263.20
366.48
1269.44
312.42
231.09
1134.94

958.25
4186.66
321.34
336.48
411.59
372.56
285.24
365.22

328.41
414.53
255.36
301.39
324.38
295.45
451.49
279.39
543.53
297.42
382.53
376.46
4491.98
543.53
325.41
581.68
324.40
295.38
345.42
272.39
388.82
46.07
296.41
141.17
324.47

245.37
284.75
296.16
326.44

271.41

0.49
1.32
1.36

1.46
1.24
3.26

3.48
3.37
4.89
1.03
1.31
0.11
0.92
1.33
2.72

2.01

4.98
2.22
0.11
1.13
0.21
3.94

0.56
2.80

1.17
2.84
3.48

1.51
2.82

1.98
1.18
0.65

1.74

0.23

0.59

1.31

2.60

0.85
0.12

3.53

0.95

1.21

1.67
0.87
2.06
0.89
1.95
2.35

3.03
2.32

3.03
0.80

1.67
1.00
2.06
0.89
4.05
3.94
3.80
1.12

2.92

0.31
3.67
1.13

2.85

0.46

1.10

2.76
0.60
2.37
1.27

1.07
2.22
1.61

4.05

0.31
3.67
0.38

2.23
4.01

3.69

1.27

4.29
1.27

4.49

3.09
2.70
3.27

4.00
3.34
3.53
0.62
1.19
3.52
4.00
1.68
2.00
2.41
0.42
1.09
0.97
3.75
5.55
1.16
1.38
3.81

2.79
3.65
1.83
4.38
1.68
0.64

1.54
1.29
1.78
0.58
4.57
4.22
4.05
3.32
1.26
0.78
0.72
1.03
0.71
3.70
2.86
1.72
2.98
9.69

7.10
1.61
0.09
3.62
4.36
3.01
2.01
3.07

0.32
1.23
4.66
3.13
1.72
2.57
3.78
1.25
0.24
3.86
0.40
5.68

3.77
3.07
2.74
2.94
0.80
3.69
3.90
2.82
1.06
4.16
1.24
4.61
8.68

2.50
3.65
3.45
2.43
2.34
4.53
3.53
4.09
0.32
4.26
3.36
0.67

3.72
2.96
4.73
3.27

3.95

2.09
3.77
1.84
1.85
1.96
2.26
4.55
2.30
3.74
2.22
2.30
0.67

0.65
3.75
3.43
2.61

1.12
2.99
1.13
1.82

1.09
3.70
1.52
1.51
2.82
4.51
3.44

1.35

1.26

5
3
4
2
2
3
4
4
5
7
2
4
6
4
18
3
4
33

13
67
6
2
3
2
8
8

4
4
2
4
3
1
9
2
12
2
3
5
67
12
3
6
3
4
5
2
6
1
2
2
2

2
2
3
6

2
0
0
2
1
0
3
1
4
2
3
1
3
3
18
1
3
15

3
58
1
0
1
2
4
4

4
0
0
4
1
0
1
0
6
1
1
2
63
6
3
3
0
2
1
2
0
1
2
1
1

2
0
2
3

104.22
57.02
72.91
64.48
23.68
29.93
86.52
58.37
101.65
120.98
74.79
41.94
110.67
107.50
537.10
47.74
78.44
662.73

212.97
1923.78
113.10
20.32
51.11
65.69
135.44
185.94

106.25
56.49
9.97
83.19
60.48
1.18
104.90
10.28
222.89
23.68
51.90
101.91
2095.89
222.89
70.55
118.24
28.67
73.30
71.04
45.43
79.29
22.56
45.43
51.12
22.56

50.84
28.76
54.80
43.08

10.28

BDDCS Applied to Over 900 Drugs

525

Inamrinone;
amrinone lactate
Indapamide
Irinotecan
Isoniazid
Isosorbide 2-mononitrate
Isosorbide 5-mononitrate
Isosorbide dinitrate
Ivabradine
Ivermectin
Ketamine
Labetalol
Letrozole
Leuprolide
Levamisole
Levobupivacaine
Levodopa
Lidocaine
Linezolid
Liraglutide
Lorazepam
Lorcainide hydrochloride
Maprotiline
Maraviroc
Melatonin
Melphalan
Meperidine; pethidine
Mepivacaine
Meprobamate
Mesna
Methadone
Methohexital
Methylergonovine
Methylphenidate
Methylprednisolone
Metoprolol
Metronidazole

Hexobarbital
Hydralazine hydrochloride
Hydrocodone
Hydrocortisone; cortisol
Hydromorphone
Hydroxychloroquine
sulfate
Hydroxyzine
Ibutilide
Idarubicin
Ifosfamide
Iloprost
Imidapril
Imipramine
Imiquimod

Generic name

mg/mL

mg
mg/mL
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg/mL
mg
mg/mL
mg
mg/mL
mg
mg/mL
mg
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg
mg/mL
mg
mg
mg
mg
mg

2.5
20
300
10
20
40
7.5
3
100
300
2.5
45
50
7.5
250
20
600
6
2
100
75
300
5
2
100
20
400
400
10
10
0.2
20
32
100
500

mg
mg/mL
mg/mL
mg/mL
g/inhalation
mg
mg
mg/g

100
0.1
1
50
5
10
50
50

0.25

mg
mg
mg
mg
mg
mg

250
100
10
20
8
200

Maximum Maximum
strength
strength
dose value dose unit

Tablets
Solution
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Solution
Tablets
Tablets
Solution
Tablets
Solution
Tablets
Solution
Tablets
Solution
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Solution
Tablets
Tablets
Tablets
Solution
Tablets
Tablets
Tablets
Tablets
Tablets

Solution

Tablets
Solution
Solution
Solution
Solution
Tablets
Tablets
Cream

Tablets
Tablets
Tablets
Tablets
Tablets
Tablets

Formulation

Oral
Injection
Oral
Oral
Oral
Oral
Oral
Oral
Injection
Oral
Oral
Injection
Oral
Injection
Oral
Injection
Oral
Injection
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Injection
Oral
Oral
Oral
Injection
Oral
Oral
Oral
Oral
Oral
(i.v.)

(epidural)

(s.c.)

(i.v.)

(epidural)

(s.c.)

(i.v.)

(i.v.)

Oral
Injection (i.v.)
Injection (i.v.)
Injection (i.v.)
Topical (aerosol)
Oral
Oral
Topical (skin.
membranes)
Injection (i.v.)

Oral
Oral
Oral
Oral
Oral
Oral

Route

0.3236
1000
10

120
100

0.2
0.08
0.1

0.1
0.1
3.22
2.4
3.4

0.4
0.0004
0.2

0.0003

0.5

0.1
0.2
0.10

0.3

0.2
0.6

0.08
0.2

0.003

0.008
0.04
0.07
0.1

0.02

0.00002

0.0006

0.002
0.009
0.0006
0.2
0.003
0.004

Dose
number

0.08
2.4
3.134

0.17
1.65
3.58
8

4
200
16
0.041
250

0.59
10
153
1.1
1.1
1.089

0.9

0.6

100
1

700
100

640
44.2
62.5
0.42
10
200

Measured
solubility
(mg/mL)

4.9
10
10

24
0.5

12
13
5

0.5
0.5
8
30
6
0.5
1
3
8

4
2.5
3.9
2

2.5

7
16.7
7

25

0.1
7
3
10
0
5
1.5
1

6
27

0.5
8
10.2

% Excreted
unchanged
in urine

Table I. (Continued)

365.84
586.69
137.14
191.14
191.14
236.14
468.60
875.12
237.73
328.41
285.31
1209.43
204.30
288.44
197.19
234.34
337.35
3751.29
321.17
370.93
277.41
513.68
232.28
305.21
247.34
246.36
218.25
142.20
309.46
262.31
339.44
233.31
374.48
267.37
171.16

187.20

374.91
384.59
497.51
261.09
360.50
405.45
280.42
240.31

236.27
160.18
299.37
362.47
285.35
335.88

MW drug

3.06
0.57
1.23

0.28
2.18
0.16
0.14
1.80
1.88
0.02

2.07
2.30

0.11
1.44
1.75
0.70

2.39
2.84
1.43

1.16
2.66
2.39
1.88
1.80

6.82
2.09
1.08

3.93

2.72
1.95
0.70

3.37
3.48
1.89
2.01
1.81
0.41
0.42

2.39
4.85
4.85

1.84
3.21
2.74
2.44

2.18
1.33

3.60
2.19
1.95

3.23
2.08
1.82
1.62

2.34
0.08
1.31
3.84
0.68

2.09

2.79
1.77
0.05
2.24
2.24
2.34

1.14
0.40
0.15
1.31

0.70

2.49

0.70
0.40
0.40
1.31

2.20

4.80
2.60

1.63
0.86
0.46

0.86
2.97

0.42
2.56

2.37

1.72

1.98
0.56
3.38
1.37

Measured
LogD74

3.50

1.98
1.00
1.27
1.61

Measured
LogP

0.27
0.58

0.43
0.65
0.68
2.94
1.46
0.23

Measured
LogS molar

3.96
2.88
1.17
3.53
2.78
0.39
1.65
2.74
1.53
1.69
2.46
3.13
3.30
1.75
3.87
0.81
1.43

3.70
3.79
0.67
0.83
0.88
2.15
3.33
8.48
1.35
2.14
4.71
5.36
1.62
3.53
1.48
2.09
3.42

2.37
4.48
4.52
3.26
1.03
0.21
2.23
2.10
0.92
1.55
4.17
1.81
1.76
2.56
1.74
1.49
0.46

2.96
2.73
0.67
0.66
0.66
0.22
3.97
5.39
2.93
2.50
1.24
0.99
1.84
3.69
2.82
1.95
0.17

0.69

4.00
3.78
0.90
0.92
2.71
1.53
5.04
3.24

3.76
2.01
3.81
2.40
4.40
0.68
2.04
2.71
1.89

1.63
0.66
1.13
1.70
0.72
4.12

CLogP

2.81
1.29
1.25
3.48
1.06
1.64

minVSLgS
37.5

4
6
3
6
6
8
6
13
2
4
4
16
2
2
5
2
5
59
3
2
1
4
2
4
2
2
2
3
2
3
3
2
5
4
4

4
4
10
2
4
6
2
3

3
4
4
5
4
4

HBA

2
1
2
1
1
0
0
3
1
4
0
16
0
1
4
1
1
54
2
0
1
1
2
2
0
1
2
2
0
1
3
1
3
2
1

1
2
5
1
3
2
0
1

1
2
0
3
1
2

HBD

102.49
108.44
74.33
96.60
96.60
130.49
57.04
173.88
32.84
106.25
61.36
464.21
10.79
33.72
114.54
33.72
70.45
1675.18
64.71
20.32
14.57
57.98
55.92
69.67
28.24
33.72
110.07
59.79
19.45
70.56
70.55
41.64
104.22
55.03
77.52

70.15

33.70
75.53
191.23
44.31
85.95
121.36
1.75
48.73

70.56
67.97
37.66
104.22
51.42
48.25

PSA

526
Benet, Broccatelli and Oprea

mg
mg
mg
mg
mg
mg
mg
mg
mg/mL

75
1
40
40
8
100
75
5
80
15
80
40
1200

40
40
400
300
400
8
60
100
1

2
0.6
5
5
15
10
100
100
50
15

Pimozide
Pramlintide acetate
Prazosin
Prednisolone
Primaquine
Prochlorperazine
Proguanil
Promazine
Promethazine
Propantheline bromide

mg
mg/mL
mg
mg
mg
mg
mg
mg
mg
mg

mg
mg
mg
mg
Active metabolite
mg
mg/mL
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg
mg
mg

0.4
0.35
0.25
0.5

mg
mg
mg/mL
mg/mL
mg
mg
mg
mg
mg
mg
mg/actuation
mg/mL
mg/mL
mg
mg
mg
mg
mg
mg
mg
mg

Nitroglycerin
Norethindrone
Norgestimate
Norgestrel
Nortilidine
Nortriptyline
Octreotide acetate
Olmesartan medoxomil
Omeprazole
Ondansetron
Orphenadrine
Oseltamivir phosphate
Oxaliplatin
Oxprenolol
Oxybutynin hydrochloride
Oxycodone
Oxymorphone
p-Aminosalicylic
acid (PAS)
Pantoprazole sodium
Paroxetine
Peoxacin
Pentamidine
Pentoxifylline
Perindopril erbumine
Phenobarbital
Phenylbutazone
Phenylephrine hydrochloride

250
60
10
2
100
10
45
0.2
50
30
0.2
20
1
2
100
30
1000
750
30
20
4

Mexiletine
Mianserin
Micafungin sodium
Midazolam hydrochloride
Minocycline hydrochloride
Minoxidil
Mirtazapine
Misoprostol
Molindone
Morphine hydrochloride
Nafarelin
Nalbuphine hydrochloride
Nalmefene hydrochloride
Naloxone
Naltrexone
Nefopam
Niacin; nicotinic acid
Niacinamide; nicotinamide
Nicardipine
Nicorandil
Nicotine

Tablets
Tablets
Tablets
Powder
Tablets
Tablets
Tablets
Tablets
Solution (with
promethazine HCl)
Tablets
Solution
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets

Capsules
Solution
Tablets
Tablets
Tablets
Tablets
Capsules
Solution
Tablets
Tablets
Tablets
Tablets
Tablets

Capsules
Tablets
Solution
Syrup
Capsules
Tablets
Tablets
Tablets
Tablets
Capsules
Solution
Solution
Solution
Tablets
Tablets
Tablets
Capsules
Tablets
Capsules
Tablets
Tablets (as
chewing gum)
Tablets
Tablets
Tablets
Tablets

Oral
Injection (s.c.)
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral

Oral
Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Injection (i.v.)

Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Oral

Sublingual
Oral
Oral
Oral

Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Topical (nasal)
Injection (i.v.)
Injection (i.v.)
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral

0.4
0.04
0.001
0.001

50

0.01
0.05

1.4
0.38
0.1
9.09
333.33

1.0

0.2
0.6

0.008

1
0.7

0.03
0.1
0.01
0.008

0.01
0.08
0.003
0.007
0.03

6
30.86
0.8
100
24
142.85

5.4
11.4
100
191

0.08
0.3
0.006
0.04

2
0.5
5.7
10

0.002
0.1
0.05
1.0

0.004
0.004
0.2
0.003
0.02
0.02

100
34
16.66
1000
7.9
4.2

0.8
0.01
0.02
0.002

0.002
0.0008

0.008
0.02
0.4

10.3
50
2.2
0.5

57.14
1
35.5
124

0.07

3.4

2
2
3.5

0.5
16
1
0.1

0
2
12
12
0
8
24
1

3
0.5
19
1.9
2

0.5
2
0
0
3
2
32
0
0
5
8
2

0
0.5
16.7

9.5
5
1
5.6
11
10
2
0.5
2
4
3
4
9.6
0
1
3

461.56
3950.46
383.41
360.45
259.35
373.95
253.74
284.43
284.43
368.50

383.38
329.37
333.37
340.43
278.31
368.48
232.24
308.38
167.21

227.09
298.43
369.51
312.46
259.35
263.39
1019.26
558.60
345.42
293.37
269.39
312.41
395.29
265.36
357.50
315.37
301.35
153.14

179.26
264.37
1270.30
325.78
457.49
209.25
265.36
382.55
276.38
285.35
1322.50
357.45
339.44
327.38
341.41
253.35
123.11
122.13
479.54
211.18
162.24

1.62

2.44
2.98

0.87

4.88
2.53
4.55
4.81
1.07

6.30

4.76

3.57
1.45
0.07

1.47
3.16
0.31

0.29

0.27

1.65
0.98

0.21
0.90
0.89

2.52
2.64
1.07

0.79
1.62
0.07
2.98

4.09

1.19
0.15
1.01
0.29
0.06
1.34
0.73
1.89

0.18

2.23
2.12
2.78

1.69

1.62
2.97
3.60
3.60

0.72
0.43

2.87

1.13
1.28
0.90

1.03

2.91

1.53
0.04
1.38

2.15
2.52

2.10

3.77

2.23

4.04

1.62
2.97

1.17

3.82

2.37
2.64

1.79
1.47
0.53
0.16

1.82
0.93
2.69
0.50
1.10
0.03

2.45
2.84
1.71
1.43

2.45
4.47
4.27
5.19

0.53
0.87
0.87
0.91
1.78
1.70

0.89

0.75
3.12
1.00
0.44
2.09
1.92
3.00
0.36

3.27
0.05
1.24

2.15
4.24

1.55
0.96
1.98
2.72

1.89

2.03
1.42
2.60
4.38
2.53
4.40
4.40
1.49

6.40

2.11
4.24
0.32
2.31
0.12
1.21
1.37
3.39
0.09

3.45
1.97
0.61
2.44
2.98
0.95
2.62
3.67
0.51
5.02
17.83
3.62
3.68
0.32
4.05
0.28
2.04
2.21
4.17

1.76
2.78
5.06
3.31
3.16
4.32
2.51
2.91
2.57
2.72
3.90
2.13
0.78
2.09
4.87
0.04
0.48
1.06

2.57
3.76
2.59
3.42
0.19
0.72
2.81
3.07
2.57
0.57
1.22
1.39
2.64
0.16
0.36
2.91
0.80
0.80
5.23
0.75
0.88
2.68
3.97
5.17
4.38
2.48
1.22
4.53
3.53
3.69
3.18
2.18
2.36
3.13
0.80
4.23
1.64
1.39
0.32

0.12
2.73
7.93
3.92
2.53
1.86
2.31
5.01
1.77
1.26
5.45
2.41
2.87
2.14
2.10
2.39
0.05
1.01
4.96
1.98
0.25

2
60
7
5
4
3
5
2
2
1

6
4
6
6
4
5
3
2
2

9
2
3
2
2
1
12
8
5
2
2
4
2
4
3
5
5
4

2
2
22
2
9
5
3
4
3
4
17
5
4
5
5
2
3
2
6
5
2

1
56
1
3
2
0
5
0
0
0

1
1
1
4
0
2
2
0
0

0
1
1
1
1
1
13
2
1
0
0
2
2
2
1
1
2
3

1
0
16
0
5
2
0
2
1
2
17
3
2
2
2
0
1
1
1
1
0

33.99
1855.80
96.10
104.22
61.59
2.92
89.44
1.75
1.75
36.48

80.15
41.89
61.72
120.17
66.77
101.91
83.96
41.56
60.00

169.35
40.83
62.44
40.83
41.64
14.57
367.50
150.96
71.04
29.66
9.97
96.67
48.49
55.34
50.80
60.22
73.98
91.37

37.08
2.05
554.51
20.12
175.38
89.15
12.29
90.45
42.21
55.71
510.46
78.27
55.71
73.98
73.98
9.97
51.07
56.49
114.03
99.54
11.42

BDDCS Applied to Over 900 Drugs

527

Roxatidine acetate HCl

Salicylic acid
Scopolamine
Secobarbital
(quinalbarbitone)
Selegiline; ()-deprenil
Sertraline hydrochloride
Sibutramine
Sildenal
Solifenacin succinate
Sparoxacin
Sufentanil
Sumatriptan succinate
Sunitinib malate
Tacrine
Tamoxifen
Tamsulosin
Temazepam
Temocapril
Temsirolimus
Tenoxicam
Terazosin
Theophylline
Thioguanine
Thiopental

Propranolol hydrochloride
Propylthiouracil
Protriptyline
Pyrazinamide
Quetiapine fumarate
Quinacrine; mepacrine
Quinidine sulfate
dihydrate
Quinine bisulfate
heptahydrate
Rabeprazole sodium
Ramelteon
Ramipril
Reboxetine
Remifentanil hydrochloride
Reserpine
Ribavirin
Ridogrel
Riluzole
Rimantadine hydrochloride
Risperidone
Rivastigmine
Rizatriptan
Ropinirole
Ropivacaine
Rosiglitazone maleate
Rotigotine

Generic name

mg
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg
mg
mg

5
100
15
100
10
200
0.05
100
50
40
20
0.4
30
4
10
20
10
600
40
1000

mg
mg
mg
mg
mg/mL
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg

20
8
10
6
1
0.25
200
5
50
100
4
6
10
5
10
8
18

mg
mg
mg
mg

mg

260

150
300
10
100

mg
mg
mg
mg
mg
mg
mg

80
50
10
500
300
100
300

Maximum Maximum
strength
strength
dose value dose unit

Tablets
Tablets
Capsules
Tablets
Tablets
Tablets
Solution
Tablets
Capsules
Capsules
Tablets
Capsules
Capsules
Tablets
Solution
Tablets
Tablets
Tablets
Tablets
Powder

Tablets
Tablets
Tablets
Tablets

Capsules
Tablets
Capsules
Tablets
Solution
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Capsules
Tablets
Tablets
Solution
Tablets
Transdermal

Capsules

Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets

Formulation

Oral
Oral
Oral
Oral
Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Injection (i.v.)

Oral
Oral
Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Injection (epidural)
Oral
Topical (skin.
membranes)
Oral
Oral
Oral
Oral

Oral

Oral
Oral
Oral
Oral
Oral
Oral
Oral

Route

0.008
0.06
0.0010
0.0002

50
0.25
42
133
53.8
0.04
5.6

0.2
0.2

0.10
0.002
0.3
0.8
0.08

0.5
0.604
0.01
0.803
24.2
8.3
0.2
50

0.02
0.008

0.7

1.1
21.4
25

0.1
0.02
0.1

0.5
0.00006
0.4

3.8
2.9
3.5

2.51
666.67
1.1

0.1
0.006
1.0

0.01
142
0.02

0.8
0.01

0.003

0.009

0.006
0.2
0.0008
0.1
0.01
0.01
0.1

Dose
number

111.1

50
1.2
50
15
94
28.57
11.1

Measured
solubility
(mg/mL)

0.1
0.2
0
7.5
12.5
10
6
22
4
0.5
0.5
8.7
0.5
1.5
4.6
0.1
10
18
0.5
0.5

2
15
6

2
20
3
0.1
14
5
1
0
0

0
0.1
1.5
10
0.1
1
17

12

18

1
1.6
0.5

0.25

% Excreted
unchanged
in urine

Table I. (Continued)

187.29
306.24
279.86
474.59
362.48
392.41
386.56
295.41
398.48
198.27
371.53
408.52
300.75
476.62
1030.31
337.38
387.44
180.17
167.19
242.34

384.90
138.12
303.36
238.29

359.45
259.35
416.52
313.40
376.46
608.69
244.21
366.34
234.20
179.31
410.50
250.34
269.35
260.38
274.41
357.43
315.48

324.43

259.35
170.23
263.39
123.12
383.52
399.97
324.43

MW drug

3.44

0.69

5.01
2.62
1.20
1.34
2.92
0.69

2.70

2.87

1.14
1.20

2.55

1.91
1.98
2.13

1.74
0.34
2.34

0.81
0.29
0.71
3.95
1.75

0.55
3.22

4.78
0.24
4.26

1.59

3.44

2.84

0.04
2.85

1.79

3.24
1.17
5.40
0.46
6.56

2.67
2.74

0.55
1.51
0.62
1.97

3.40

1.15

0.08
2.52

1.25
4.14
2.43

1.76

1.82

1.91
1.82

1.20
1.09
1.36
0.59

Measured
LogD74

0.32
4.64
0.02

2.19

2.71

3.95
0.93

1.49

2.90

2.26
0.98
1.97

4.03

2.70
2.90

3.04

1.85
3.72
1.85

0.60

3.48

Measured
LogP

0.71
2.15
0.72
0.91
0.97
1.15
1.85

Measured
LogS molar

2.80
2.19
0.29
2.16
3.02
5.35
5.59
1.98
4.68
0.61
3.59
0.74
3.00
3.27
6.82
2.17
2.34
2.10
0.67
1.61
2.18
0.03
1.70
2.98

2.32
2.99
2.19
4.17
3.16
0.67
3.23
0.96
2.58
0.12
4.42
2.96
3.58
1.98
9.52
0.17
3.71
1.87
0.79
3.26

2.08
2.49
1.54
3.26
1.96
3.86
2.85
4.54
3.24
3.96
2.71
2.10
0.99
2.80
3.16
3.02
4.54

3.73
3.49
1.27
2.11
3.15
5.80
0.90
3.58
2.72
1.85
3.49
1.56
1.19
0.33
3.25
3.80
2.44
2.62
0.20
1.72
2.94

2.79

2.75
0.97
4.87
0.68
2.99
6.72
2.79

CLogP

2.85

1.11
1.83
1.10
0.57
3.69
2.09
2.67

minVSLgS
37.5

1
1
1
7
2
7
3
3
3
2
2
6
3
5
14
5
8
3
3
2

4
3
4
3

5
2
5
4
4
8
7
5
3
1
4
2
3
2
2
5
2

3
1
1
3
5
4
4

HBA

0
1
0
1
0
3
0
2
3
1
0
2
1
2
4
2
1
1
3
2

1
2
1
2

1
1
2
1
0
1
4
1
1
1
0
0
1
1
1
1
1

2
2
1
1
1
1
1

HBD

1.18
14.57
1.18
105.18
29.42
102.79
29.11
67.24
80.53
37.91
10.28
107.38
51.32
101.91
253.80
104.05
95.48
61.90
76.09
65.69

70.19
63.70
59.59
83.96

70.73
41.95
101.91
41.58
74.45
114.49
146.67
72.68
47.02
27.97
53.60
29.73
39.11
33.72
33.72
71.34
24.05

43.08

46.24
46.21
14.57
66.73
43.01
34.79
43.08

PSA

528
Benet, Broccatelli and Oprea

200
250
50
20
500
2
60
50
10
4
4
0.5
10
5
200
5
5
1000
450
250
20
60.8

150
120
1
1
10
25
1.4
2.5
300
5
10
100
7.5

Thioridazine
Ticlopidine
Tilidine; tilidate
Timolol
Tinidazole
Tolterodine
Toremifene
Tramadol
Tranylcypromine sulfate
Triamcinolone
Triamcinolone acetonide
Triazolam
Triuoperazine
Trihexyphenidyl (benzhexol)
Trimetrexate glucuronate
Tropisetron
Urapidil
Valacyclovir
Valganciclovir; valcyte
Valproic acid
Vardenal
Vasopressin

Venlafaxine hydrochloride
Verapamil hydrochloride
Vinblastine
Vincristine
Vinorelbine tartrate
Vitamin B6 (pyridoxine)
Vitamin D3 (cholecalciferol)
Vorozole
Zidovudine
Zolmitriptan
Zolpidem tartrate
Zonisamide
Zopiclone

mg
mg
mg/mL
mg/mL
mg/mL
mg
mg
mg
mg
mg
mg
mg
mg

mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg
mg
g/mL

Tablets
Tablets
Capsules
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Powder
Capsules
Solution
Caplets
Tablets
Tablets
Tablets
Solution (20 units
per mL)
Tablets
Tablets
Solution
Solution
Solution
Capsules
Tablets
Tablets
Capsules
Tablets
Tablets
Capsules
Tablets
Oral
Oral
Injection (i.v.)
Injection (i.v.)
Injection (i.v.)
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral

Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Injection (i.v.)
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Injection (s.c.)
0.03
0.1
0.0007
0.6
0.0008
0.2
0.1
0.04
0.0008
0.002
0.02
0.002

2.74
20
12
0.38
48
0.08
0.114
0.045
50
10
50
11
19
174
70
1.3
0.11
0.1

0.0005
0.06
0.05
0.001
0.002
0.5
0.3

25
20
23
0.8
0.12

0.001
0.64

572
0.75
10
10
1000
222
0.1

0.02
0.03
0.8
0.7

0.8

8
2.8
8
0.5
22
4.5

4.6
1.5
0.5
15
11

1.8
4
5

20
8
15
0.5

1
1
2

0.5
0.1
15
22.5
1
0.1
20

277.41
454.61
811.00
824.98
778.95
169.18
384.65
324.78
267.25
287.36
307.40
212.23
388.82

370.58
263.79
273.38
316.43
247.27
325.50
405.97
263.38
133.19
394.44
434.51
343.22
407.50
301.48
369.43
284.36
387.49
324.34
354.37
144.22
488.61
1084.25

1.03
1.16
1.13
2.42
3.51

0.31
3.05
1.91
1.92
0.11
0.12
3.59

0.44
3.69
3.58
3.88
0.91
1.48
0.87
1.41
1.31
0.27
0.70
2.05
3.65
4.04

2.06
1.09
1.43
3.03

2.57

0.08
2.35
0.10
0.90
1.50

3.69
2.57

2.05
0.13

0.65
2.02

0.69
1.16
2.30
1.63
3.14

1.91
0.33

3.55
3.37

0.05

0.77

3.79
3.70

2.75

1.60

1.16
2.53
2.42
5.03
4.82
1.63

2.63

1.83
0.35

5.90

6.00
4.39
3.76
1.21
0.32
5.24
6.53
3.10
1.48
0.71
2.21
2.62
4.69
5.15
1.84
2.88
2.44
1.22
2.18
2.76
2.23
3.82
3.27
4.47
5.23
4.04
5.94
0.35
9.48
2.20
0.04
1.29
3.03
0.36
1.25

3.53
3.48
2.77
0.74
1.71
2.28
4.75
0.59
0.33
3.07
4.17
4.21
3.80
1.94
3.54
1.94
3.74
1.59
1.54
1.45
4.03
2.25
1.52
4.11
6.97
6.35
6.71
0.75
6.71
4.16
2.31
1.03
4.20
1.30
2.84

3
6
9
9
8
4
1
4
6
2
3
3
6

2
1
2
7
5
2
2
3
1
6
6
3
3
2
8
2
6
7
9
2
7
16
1
0
3
3
2
3
1
0
2
2
0
1
0

0
0
0
2
0
1
0
1
1
4
2
0
0
1
3
1
1
3
4
1
1
15
32.84
56.29
152.61
170.88
130.05
78.23
22.56
50.83
127.30
56.78
29.96
88.84
79.29

1.75
1.18
28.24
75.98
91.72
24.05
10.28
32.84
27.97
126.78
99.25
33.27
2.92
23.73
117.41
42.21
63.11
144.80
167.36
40.83
104.88
504.48

BDDCS Applied to Over 900 Drugs

529

10-Hydroxy-carbamazepine
6-Methoxy-2-naphthyl-acetic
acid
Acitretin
Adapalene

Calcitriol
Capsaicin
Carbamazepine
Carbamazepine
10,11-epoxide
Carvedilol
Cefditoren pivoxil
Cefpodoxime proxetil
Celecoxib
Chlorzoxazone
Ciclesonide
Cilostazol
Cinacalcet
Cisapride
Citalopram
Cladribine
Clofazimine
Clobrate
Clopidogrel bisulfate
Clotrimazole
Clozapine

g
mg
mg
Active metabolite

mg
mg
mg
mg
mg
mg/inhalation
mg
mg
mg
mg
mg/mL
mg
mg
mg
mg
mg

25
200
200
200
500
0.16
100
90
20
40
1
50
500
75
10
100

mg
Active metabolite
mg
mg
mg
mg
mg/mL
mg
mg/mL
mg
mg/mL
mg
mg
mg
mg
mg
mg
g/mL
mg
mg
mg
mg
mg
mg
mg
g/mL

mg
mg

Active metabolite
Active metabolite

Maximum strength
dose unit

0.5
179
300

300
50
250
400
2
50
3.33
125
1
30
250
50
10
300
80
457
200
75
200
50
125
10
0.5
0.05

200

25
6

Generic name

Albendazole
Albendazole sulfoxide
Allopurinol
Altretamine
Aminoglutethimide
Amiodarone hydrochloride
Amphotericin B
Amprenavir
Anidulafungin
Aprepitant
Argatroban
Aripiprazole
Armodanil
Artemether
Astemizole
Atazanavir sulfate
Atorvastatin calcium
Azelastine hydrochloride
Bevantolol
Bexarotene
Bezabrate
Bicalutamide
Bosentan
Buspirone
Cabergoline
Calcipotriene; calcipotriol

Maximum
strength dose
value

Tablets
Tablets
Tablets
Capsules
Tablets
Solution
Tablets
Tablets
Tablets
Tablets
Solution
Capsules
Capsules
Tablets
Tablets
Tablets

Capsules
Cream
Tablets

Tablets
Capsules
Tablets
Tablets
Solution
Capsules
Solution
Capsules
Solution
Tablets
Tablets
Tablets
Tablets
Capsules
Tablets
Solution
Tablets
Capsules
Capsules
Tablets
Tablets
Tablets
Tablets
Solution

Tablets

Capsules
Cream, gel, solution

Formulation

Oral
Oral
Oral
Oral
Oral
Topical (nasal)
Oral
Oral
Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Oral

Oral
Oral
Oral
Oral
Injection (i.v.)
Oral
Injection (i.v.)
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Oral
Oral
Ophthalmic
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Topical (skin,
membranes)
Oral
Topical
Oral

Oral
Topical (skin.
membranes)
Oral

Route

2.3

0.7
0.1
0.04
0.05

5.9
13
34

200

0.001
0.05078
0.003
0.0118

10
10
2.7
160
8.0
3.2
133
3.6
30
5.2

0.01
0.08
0.3
0.005
0.25
0.0002
0.003
0.1
0.0027
0.031

12
4.7

40
500
1.9

0.005
0.001
0.0214

0.06
0.256
0.1

4.3

15686

0.0000204
0.1843

1200

0.0001

5.0

2.1

Dose
number

0.569

0.045

Measured
solubility
(mg/mL)

5
0.5

12
18
0.2
11

0.1

1
5
0
2
0.5
0

8
0
0.5
0.5

2
0.1
3
0.5

0.5
7
1
2
8
0.01
40

0
3.5
1
0.5
0
16
0.5
8

0
1
12
0.5

27
1

% Excreted
unchanged
in urine

406.49
620.73
557.61
381.38
169.57
540.70
369.47
357.42
465.96
324.40
285.69
473.41
242.70
321.83
344.85
326.83

416.65
305.42
236.28
252.28

265.34
281.34
136.11
210.28
232.28
645.32
924.10
505.64
1140.27
534.44
508.64
448.40
273.36
298.38
458.58
704.87
558.66
381.91
345.44
348.49
361.83
430.38
551.63
385.51
451.62
412.62

326.44
412.53

254.29
216.24

MW drug

3.80
5.06
4.44

5.68

4.61
3.89
3.27
4.88
2.83
6.43
5.09
3.55
5.24
4.02

4.80
3.23

3.41
0.02
7.48
3.60

4.19

2.45
0.69

2.63

4.93
5.74
4.26

3.71
2.97
3.40

3.00

3.27

7.44

5.70

7.80

2.96
3.97
4.10
4.36

6.65

0.55
2.73

6.40
7.88

Measured
LogP

2.38

3.75

Measured
LogS molar

Table II. Measured and In Silico Data for 265 BDDCS Class 2 Drugs

2.99

3.60

3.39
0.74
0.24

2.45
0.69

3.39

0.17

1.96
3.00

3.88

3.20

1.41
2.54

0.55

2.85

1.26
0.30

Measured
LogD74

3.46
3.46
0.63
1.67
0.77
8.95
3.65
3.29
2.20
4.60
0.57
5.31
0.94
3.05
6.09
5.92
4.46
4.01
3.00
8.19
3.70
2.71
4.17
2.19
4.77
5.27

3.54
3.28
1.18
3.02
2.35
5.40
6.40
5.03
10.68
5.28
1.80
4.64
2.82
3.35
5.40
7.38
6.47
2.37
3.15
4.74
3.79
4.32
5.38
3.50
4.28
5.58

4.30
6.88
4.79
4.47
1.77
6.25
4.87
3.12
4.57
2.83
2.15
5.84
1.63
3.83
5.07
4.37

4.04
2.71
0.80
4.37
2.51
5.25
3.53
6.35
3.81
3.13
0.91
7.70
3.02
4.21
5.25
3.71

6.04
4.00
2.38
0.24

6.07
9.15

5.07
5.78

6.35
4.49
3.32
3.00

1.21
2.51

CLogP

3.15
2.29

minVSLgS 37.5

5
9
10
3
2
6
5
1
6
3
7
4
3
2
1
4

3
3
1
1

3
3
3
6
3
3
17
6
17
5
9
4
2
5
4
7
5
3
5
2
4
5
9
6
4
3

3
3

2
3

HBA

3
2
2
1
1
1
1
1
2
0
3
1
1
0
0
1

3
2
1
1

2
2
2
0
2
0
12
3
14
2
6
1
1
0
1
5
4
0
2
1
2
2
2
0
2
3

1
1

2
1

HBD

78.42
176.19
183.53
78.91
42.53
103.75
81.66
14.57
88.69
28.67
112.88
34.09
36.17
28.24
10.81
25.63

67.68
64.82
46.81
55.61

65.55
65.55
70.47
33.35
78.79
37.97
347.83
139.36
415.56
78.12
192.20
43.70
64.62
49.50
35.37
186.22
119.06
33.17
64.45
40.83
82.78
110.56
142.96
60.25
118.24
67.68

49.94
49.94

32.78
49.94

PSA

530
Benet, Broccatelli and Oprea

Conivaptan hydrochloride
Cyclosporine
Cyproterone acetate
Danazol
Dapsone
Darunavir
Dasatinib
Daunorubicin
Delavirdine
Desloratadine
Diazoxide
Dicoumarol
Diunisal
Diloxanide furoate
Dipyridamole
Disulram
Docetaxel
Domperidone
Donepezil
Dronabinol;
tetrahydrocannabinol
Dronedarone
Drospirenone
Dutasteride
Ebastine
Efavirenz
Entacapone
Eplerenone
Erlotinib hydrochloride
Estazolam
Ethchlorvynol
Etizolam
Etodolac
Etomidate
Etoricoxib; arcoxia
Etravirine
Exemestane
Ezetimibe
Febuxostat
Felodipine
Fenobrate
Flufenamic acid
Flunarizine
Fluphenazine hydrochloride
Flurbiprofen
Flutamide
Fluticasone propionate
Folic acid
Fosamprenavir calcium
Fosinopril
Fulvestrant
Getinib
Gembrozil
Gliclazide
Glimepiride
Glipizide
Glyburide; glibenclamide
Griseofulvin
Haloperidol
Ibuprofen
Idebenone

mg/ml
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg

mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
g/inhalation
mg
mg
mg
mg/mL
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg

5
100
50
200
100
600
70
5
200
5
100
100
500
500
75
250
40
20
10
10

400
3
0.5
10
600
200
50
163.9
2
750
1
600
2
120
100
25
10
80
10
145
100
10
10
100
125
50
5
700
40
50
250
600
80
4
10
6
500
20
800
180

Tablets
Tablets
Capsules
Tablets
Capsules
Tablets
Tablets
Tablets
Tablets
Capsules
Tablets
Tablets
Solution
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Capsules
Tablets
Tablets
Tablets
Capsules
Capsules
Suspension
Tablets
Capsules
Tablets
Solution
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Capsules
Capsules

Solution
Capsules
Tablets
Capsules
Tablets
Capsules
Tablets
Solution
Caplets
Tablets
Capsules
Tablets
Tablets
Tablets
Tablets
Tablets
Solution
Tablets
Tablets
Capsules
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Topical (nasal)
Oral
Oral
Oral
Injection (i.m.)
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral

Injection (i.v.)
Oral
Oral
Oral
Oral
Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Injection (i.v.)
Oral
Oral
Oral

6.0
2.2
84

0.037
0.038

53
3.9
13
9.0
7.3
200
588
126
82
13

0.0095
0.00051
0.0016
0.31
0.022
0.001
0.0017
0.019
0.0039
0.0012
0.004

25
40
725
15
2.4
1.3

3.4

240

1.6
5.3

480
48

3.2

0.013
0.001
0.0008
0.0265
0.0165
0.031

0.01
0.045
0.14

0.4
0.0015

0.005
0.0166

0.5

13
14

43
5.0

988
260
2.7
3.1

0.0392
0.00081
0.000077
0.15
0.128

0.007
0.2
0.0065
0.006
0.0029

50
95
889
2.0
16

0.15
0.008
0.0021
0.0009
0.2
0.15

0
0
0.1
2
0.5
0.5
0
4.5
0
0.3
1
0.5
0.5

0
0.1
0.5
2
0.5
0.2
3
0.3
4
0.05
0.3
1
2
0.5
0
1
2
3
0.25
0.1
7
0.2
0.1
2.9
0.5
3

15
1.2
0.1
0.5
2.5
5
35
0.5
6
1
0.1
0
5
0
10.6
0.5

1
0.1
1

556.77
366.50
528.54
469.67
315.68
305.29
414.50
393.45
294.75
144.60
342.85
287.36
244.30
358.85
435.29
296.41
409.44
316.38
384.26
360.84
281.24
404.51
437.53
244.27
276.22
500.58
441.41
585.62
563.68
606.79
446.91
250.34
323.42
490.63
445.54
494.01
352.77
375.87
206.29
338.45

498.59
1202.64
416.95
337.47
248.31
547.68
488.02
527.53
456.57
310.83
230.67
336.30
250.20
328.15
504.64
296.54
807.90
425.92
379.50
314.47

4.01
3.73

5.09

4.46
5.99
5.44
3.28
4.41
5.78
5.42
4.12
4.92
5.61

4.39
5.58
5.65
4.03
4.39
4.22

4.46
3.73
3.41

2.99
5.29

4.80
4.26

3.05

4.86
3.17
5.09
4.85
5.12

4.13
5.75
6.61
3.19
3.42

3.55
5.18
5.30
5.57
3.09
3.56

2.18
4.30
3.97

1.91

1.36

4.85

0.52

4.16
3.35

5.25
5.78

3.86

3.81
3.05

3.78

6.97

0.40
1.41
2.18
3.16
0.81

1.33
0.07

2.32

4.80
2.06
4.90
3.48
0.91
4.06

1.14
3.05

2.06

0.85

2.78

3.33

3.71
3.88

1.08
1.86
0.76

1.83

0.97

2.92

3.90

3.88

1.81
2.07
4.44
1.96

1.83

0.97

2.95

5.00
14.36
3.96
3.93
0.89
2.89
2.88
0.84
2.41
3.83
1.42
3.66
4.40
3.09
1.49
3.88
4.08
4.27
4.60
7.24
8.57
2.84
4.94
6.94
4.67
1.76
0.29
4.34
2.29
1.57
2.87
3.43
2.67
2.35
5.22
3.28
3.96
4.40
5.30
5.23
5.53
6.34
4.12
3.75
3.34
3.80
2.31
3.04
7.45
7.35
5.60
3.94
1.09
3.96
2.57
4.24
1.91
3.85
3.68
3.42

6.73
10.73
4.83
4.54
2.71
5.44
4.70
3.89
4.80
2.42
2.00
3.06
2.17
4.03
4.21
4.19
7.05
4.31
4.10
5.91
4.24
4.11
6.05
5.87
3.99
2.73
4.02
5.20
3.73
2.16
3.82
2.81
3.49
4.52
6.76
3.95
5.56
3.59
4.73
5.47
3.41
5.69
4.11
2.76
3.17
4.82
2.59
0.53
5.95
8.28
4.77
3.15
2.98
5.70
4.49
5.47
3.19
3.68
2.31
4.81

5
2
2
3
2
6
4
7
3
1
3
3
2
4
6
2
3
5
3
3
3
2
4
2
3
4
12
8
5
3
7
3
4
5
6
5
6
3
2
5

3
12
3
2
4
7
8
11
6
2
3
4
3
2
12
0
10
3
4
2
1
0
2
0
1
2
0
1
0
1
0
2
0
0
2
0
2
1
1
0
2
0
1
1
1
1
6
4
1
2
1
1
2
3
3
3
0
1
1
1

2
5
0
1
2
3
3
5
3
1
1
2
2
0
4
0
5
2
0
1

89.77
45.34
65.39
28.24
41.34
128.04
81.19
70.25
33.27
22.56
33.27
63.59
37.88
57.25
108.94
36.54
64.57
78.88
68.70
54.44
54.80
2.35
25.48
40.83
76.69
86.17
219.42
189.86
115.00
63.81
62.63
49.94
89.39
137.24
138.28
126.89
72.65
42.01
40.83
76.69

75.90
290.07
63.61
45.90
92.10
148.15
101.85
200.34
110.60
24.82
61.41
101.12
63.70
55.94
134.70
2.35
240.13
66.80
37.66
31.98

BDDCS Applied to Over 900 Drugs

531

Mizolastine
Modanil
Mometasone furoate
Montelukast sodium
Mycophenolate
Mycophenolate mofetil
Nabumetone
Nalidixic acid
Naproxen
Nateglinide
Nefazodone
Nelarabine
Nelnavir
Nevirapine
Nifedipine
Nifurtimox

Loratadine
Losartan potassium
Lovastatin
Mebendazole
Mefenamic acid
Meoquine
Meloxicam
Mercaptopurine;
6-mercaptopurine
Mesalamine; mesalazine
Metaxalone
Methaqualone
Miconazole

Iloperidone
Imatinib mesylate
Indinavir sulfate
Indobufen
Indomethacin
Indoramin
Irbesartan
Isotretinoin;
13-cis-retinoic acid
Isradipine
Itraconazole
Ixabepilone
Ketanserin
Ketoconazole
Ketoprofen
Lamotrigine
Lansoprazole
Lapatinib ditosylate
Latanoprost
Leunomide
Lofepramine
Lopinavir

Generic name

500
750
1000
500
120
100
5
625
200
20
250

mg
mg
g/activation
mg
Active metabolite
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg
mg

mg
mg
mg
mg

1200
800
500
1200

10
200
200
10

mg
mg
mg
mg
mg
mg
mg
mg

mg
mg
mg/mL
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg

5
100
1.915
40
200
75
200
30
250
0.5
100
70
200

10
100
40
100
250
250
15
50

mg
mg
mg
mg
mg
mg
mg
mg

Maximum strength
dose unit

12
400
400
200
50
25
300
40

Maximum
strength dose
value

Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Solution
Tablets
Tablets
Capsules
Tablets

Tablets
Tablets
Powder
Tablets

Tablets
Tablets
Tablets
Cream, suppository

Capsules
Capsules
Solution
Tablets
Tablets
Capsules
Tablets
Capsules
Tablets
Solution
Tablets
Tablets
Capsules (with
50 mg ritonavir)
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets

Tablets
Capsules
Capsules
Tablets
Tablets
Tablets
Tablets
Capsules

Formulation

Oral
Oral
Oral
Oral
Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral

Oral
Oral
Oral
Topical (skin,
membranes)
Oral
Oral
Topical (aerosol)
Oral

Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral

Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Oral
Oral
Ophthalmic
Oral
Oral
Oral

Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral

Route

5.0

0.012

0.1
0.006

0.043
0.015
0.054
0.115
0.322

0.013

8.0
13

47
200
74
17
1.5

3.1

4.8
11
6.7
5.4

13

0.08

1
0.3
0.3
0.89

8.0
8.3
400

0.005
0.048
0.0004

17

3.2
116
1.7
4.7
124
1000

0.05
0.0069
0.18
0.17
0.00097
0.001
0.05
0.023

15

0.08

2.5
400000

80

0.0025

0.008
0.000001

1.6
1.6
107

Dose
number

0.03
1
0.015

Measured
solubility
(mg/mL)

0.01
1

0.5
13
0.1
6.6

5
8
0.5
0.2
0.5
0
0

7
2
0.2
0

1
9
0.2
22

5
12
10

1
4
2.2

0
0.03
5.6
0.5
3
0.5
10
0
1

13
15
5
2.5
0.5

0.5
5

% Excreted
unchanged
in urine

Table II. (Continued)

432.50
273.36
521.44
586.20
320.35
433.51
228.29
232.24
230.27
317.43
470.02
297.27
567.80
266.31
346.34
287.30

153.14
221.26
250.30
416.14

382.89
422.92
404.55
295.30
241.29
378.32
351.41
152.18

371.40
705.65
506.71
395.44
531.44
254.29
256.10
369.37
581.07
432.61
270.21
418.97
628.82

426.49
493.62
613.81
295.34
357.80
347.46
428.54
300.44

MW drug

3.43
4.76

2.47

4.00
4.18
3.63
3.30
2.99

4.52

2.19
2.87
2.92
2.67

4.47

3.48

1.81
2.20

5.00

3.08
1.59
3.18

2.42
2.50
5.34

2.80

0.20
2.37
3.38
0.59
1.70

2.50
6.34

3.20

0.72
0.10
0.39

4.26
2.42

4.26
2.83
5.12
3.02
0.01

5.20

6.57

2.18
4.05
0.01
0.19
2.36

3.67
3.27

0.70
0.77
2.29
1.00
4.23

Measured
LogD74

5.20

3.29
4.35
3.12

3.90
4.89
3.15
3.18
5.58
5.76
3.94
4.07

4.88
3.98
6.00

4.28
5.66

6.30
4.67
8.85

3.73

4.27
3.23

2.92

4.15
2.69
4.61
5.16

Measured
LogP

Measured
LogS molar

5.28
2.92
5.87
7.75
3.44
4.67
3.51
1.88
2.50
3.53
5.94
1.56
6.89
3.15
3.66
2.02

1.97
2.49
3.83
5.83

5.32
2.04
4.95
4.00
3.36
3.12
2.15
1.74

4.14
8.44
5.51
5.10
5.99
2.82
2.75
3.74
7.19
6.14
2.99
6.58
7.32

3.87
5.77
6.21
3.20
3.93
3.86
2.82
4.80

minVSLgS 37.5

2.84
0.94
4.12
8.47
2.29
2.98
2.98
1.02
2.82
4.30
5.73
0.46
5.84
2.65
3.13
0.02

1.06
2.15
3.65
5.81

5.05
4.10
4.08
3.08
5.29
3.67
2.29
0.82

3.92
5.99
3.08
3.00
3.64
2.76
2.53
2.60
5.97
3.60
2.32
7.29
6.10

4.27
4.53
3.68
3.27
4.18
2.84
6.04
6.74

CLogP

5
2
4
4
5
6
2
5
3
3
5
9
5
4
5
6

4
2
2
2

2
5
3
4
3
3
5
3

5
9
6
4
6
3
5
4
7
4
2
3
5

5
7
7
3
4
2
5
2

HBA

1
1
1
2
2
1
0
1
1
2
0
4
4
1
1
0

3
1
0
0

0
2
1
2
2
2
2
2

1
0
3
1
0
1
2
1
2
3
1
0
4

0
2
4
1
1
2
1
1

HBD

55.05
64.62
89.90
73.63
99.87
96.07
27.38
69.92
49.94
73.68
43.72
112.88
112.29
53.60
112.85
104.39

91.37
50.74
28.78
19.61

38.48
86.79
76.69
83.82
54.80
47.38
104.05
44.70

105.96
84.66
115.27
70.53
57.83
59.10
88.97
61.94
104.31
94.74
55.88
20.02
131.37

61.00
79.59
123.40
59.98
68.78
47.99
82.47
40.83

PSA

532
Benet, Broccatelli and Oprea

mg
mg
mg
mg/mL
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg

mg
mg
Active metabolite

mg
mg
mg

45
20
4
40
10
30
600
50
250
500
500
200
300
10
500
0.5
180
15
40
60
400
1000
2
150
300
100
50
5
400
0.05
500

80
2

200
100
800

Pioglitazone
Piroxicam
Pitavastatin
Posaconazole
Prasugrel
Prazepam
Praziquantel
Prednisone
Primidone
Probenecid
Probucol
Progesterone
Propafenone hydrochloride
Propofol
Propoxyphene napsylate
Proscillaridin
Pyrantel pamoate
Quazepam
Quinapril
Raloxifene; keoxifene
Raltegravir potassium
Ranolazine
Repaglinide
Rifabutin
Rifampin
Ritonavir
Rofecoxib
Romidepsin
Runamide
Salmeterol xinafoate
Saquinavir
methanesulfonate
Simvastatin
Sirolimus
SN-38; 7-ethyl-10hydroxycamptothecin
Sorafenib tosylate
Spironolactone
Sulfamethoxazole

mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg/mL
g
mg
mg
mg
mg
mg
mg/g

200
2
100
30
10
20
6
5
40
600
30
30
600
6
4
50
1
100
500
300
10

Nilotinib
Nilvadipine
Nimesulide
Nimodipine
Nitrazepam
Nitrendipine
Norelgestromin
Norethindrone acetate
Olanzapine
Oxaprozin
Oxatomide
Oxazepam
Oxcarbazepine
Paclitaxel
Paricalcitol
Pentazocine
Pergolide
Perhexiline
Phenacetin
Phenytoin sodium
Pimecrolimus

Tablets
Tablets
Tablets

Tablets
Tablets

Tablets
Capsules
Tablets
Suspension
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Capsules
Tablets
Emulsion
Tablets
Capsules
Caplet
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Capsules
Capsules
Capsules
Tablets
Solution
Tablets
Powder
Capsules

Capsules
Tablets
Tablets
Capsules
Capsules
Capsules
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Solution
Capsules
Tablets
Tablets
Tablets
Tablets
Tablets
Cream

Oral
Oral
Oral

Oral
Oral

Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Oral
Oral
Topical (skin,
membranes)
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Injection (i.v.)
Oral
Topical (aerosol)
Oral
4.5

0.0449

0.022
0.392

18
8.2

11

25

0.08
0.03

27

2.0

0.1
0.059

3.2

160
18

1.4

0.19

0.001
0.013

0.5

114
13

0.007
0.093
0.164
0.0196
102

30
6.0
1.5
1.7

11

0.004
0.4
0.133
0.6

0.00005

0.0073

6667
2.7
60

4.0
16
1.4
2.8
2.7
28

0.005
0.01
1.7
0.043
0.045
0.085

0.00006
0.73
0.02

6.2
29
48
1.6
36

0.0013
0.014
0.0025
0.0254
0.0022

0
0.5
14

10
2
0.5

1
2.5
2

3.1
0.1
9
6
1.5
10
7
3.5
1

0
0.5
0.5

0.1
1
0
2
3
35
1.2

0.5
5

2
0

5
0
15

0
7
0.5
0
0.5

4
0
2
0.5
0.5
0.5

464.83
416.58
253.28

418.58
914.20
392.42

356.45
331.35
421.47
700.80
373.45
324.81
312.42
358.44
218.26
285.36
516.86
314.47
341.45
178.28
367.54
530.66
206.31
386.80
438.53
473.60
444.43
427.55
452.60
847.03
822.96
720.96
314.36
540.71
238.20
415.58
670.86

529.53
385.38
308.31
418.45
281.27
360.37
327.47
340.47
312.44
293.33
426.57
286.72
252.28
853.93
416.65
285.43
314.50
277.50
179.22
252.28
810.47

2.26
0.89

4.68

4.28
2.81

4.70
4.14

3.20

4.03

2.48

3.79

3.87

1.46
0.91
3.21

3.73

3.98

3.61

3.50

3.65

5.64
4.56

2.62

4.65
3.56
3.04
4.27

4.91
2.89
3.43
2.56

7.15

3.06

1.58
2.47

6.67
2.39
4.14

4.66

3.31

3.00
4.19
5.42
2.24

1.79
3.05
2.25
2.88
2.70

3.80

4.83
4.49
2.24
4.00
3.80
3.47

5.47
4.34
5.22
4.04
5.21

2.26

4.68

1.32

0.45

3.87
2.26

2.48

4.16

3.73
2.44
1.46
0.84
0.26
10.40

0.20
1.50

2.47

0.83
3.97
3.93

1.03
3.39
2.24
1.25
6.83

2.86
2.16

1.10

4.48
7.04
1.97
5.46
2.65
0.56

5.95
4.58
2.12

3.53
1.89
3.59
4.11
3.43
3.93
3.36
1.66
0.88
3.37
10.97
3.78
3.64
3.93
5.32
3.66
3.03
3.20
1.74
6.86
1.16
1.01
5.30
4.73
3.71
4.94
1.80
3.44
0.51
3.06
4.73

1.08
0.23
1.51
7.92
4.26
4.53
3.89
3.57
2.59
2.36
8.32
4.25
2.21
3.29
0.95
5.09
1.01
4.62
1.82
5.56
3.79
4.58
2.42
5.36
4.36
8.08
2.83
4.16
2.26
3.01
6.91
5.15
9.32
4.37

5.84
3.04
3.21
4.00
2.32
3.73
4.10
3.93
3.01
2.95
5.62
2.31
1.21
4.73
5.69
4.67
4.40
7.15
1.77
2.09
5.30

7.56
4.10
3.01
4.68
3.51
4.20
4.56
4.89
3.79
3.58
5.49
3.55
3.18
7.35
6.29
2.06
3.98
1.41
2.16
3.25
8.00

3
3
4

3
12
5

4
5
5
9
3
2
2
5
2
4
2
2
4
1
2
7
2
1
5
5
7
6
5
13
14
6
3
5
3
5
7

6
6
4
6
4
5
3
2
4
3
3
3
2
10
3
2
1
1
2
2
10

3
0
2

1
3
2

1
2
3
1
0
0
0
2
2
1
2
0
2
1
1
4
0
0
2
2
3
2
2
5
6
4
0
4
1
4
5

2
1
1
1
1
1
2
1
1
1
1
2
1
4
3
1
1
1
1
2
2

99.32
63.61
102.81

76.69
204.17
101.58

70.46
104.05
96.19
98.43
46.82
28.76
38.89
99.93
65.69
79.53
45.74
36.54
64.51
22.87
41.64
135.51
10.79
10.48
101.91
74.29
150.45
75.66
83.65
216.49
233.54
151.55
63.82
158.44
73.11
91.35
178.75

87.75
131.55
105.36
121.64
86.30
112.85
57.94
45.34
25.63
60.49
35.16
64.71
65.09
235.84
67.68
24.05
15.14
14.57
41.65
65.69
163.34

BDDCS Applied to Over 900 Drugs

533

Sulfasalazine
Sulnpyrazone
Sulindac
Sulindac sulde
Tacrolimus
Tadalal
Tegaserod maleate
Telithromycin
Telmisartan
Temozolomide
Teniposide
Terbinane
Terfenadine
Testolactone
Testosterone
Tetrabenazine
Thalidomide
Thiabendazole
Thyroxine; levothyroxine
Tiagabine hydrochloride
Tiaprofenic acid
Tibolone
Tipranavir
Tizanidine
Tolazamide
Tolbutamide
Tolcapone
Tolfenamic acid
Tolmetin
Tolvaptan
Torsemide, torasemide
Trandolapril
Trazodone
Treprostinil
Tretinoin
Triamterene
Triclabendazole
Trimipramine maleate
Ursodiol; ursodeoxycholic
acid
Valdecoxib; bextra
Vitamin A (retinol)
Vitamin D2 (ergocalciferol)
Voriconazole
Warfarin
Zarlukast
Zaleplon
Zileuton
Ziprasidone hydrochloride

Generic name

mg
mg
mg
mg
mg
mg
mg
mg
mg

5
20
6
400
80
250
10
250
60
50
40
25
200
500
0.3
16
300
2.5
500
6
500
200
200
200
600
30
100
4
300
10
10
100
250
100
500

20
110
1.25
200
10
20
10
600
80

Maximum strength
dose unit

mg
mg
mg
Active metabolite
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg
mg
mg

500
200
200

Maximum
strength dose
value

Tablets
Tablets
Capsules
Tablets
Tablets
Tablets
Capsules
Tablets
Capsules

Capsules
Tablets
Tablets
Tablets
Tablets
Capsules
Solution
Tablets
Tablets
Tablets
Capsules
Tablets
Capsules
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Capsules
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Solution
Capsules
Capsules
Tablets
Tablets
Tablets

Tablets
Capsules
Tablets

Formulation

Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral

Oral
Oral
Oral
Oral
Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Injection (s.c.)
Oral
Oral
Oral
Oral
Oral

Oral
Oral
Oral

Route

2.0

0.8

7.2
7.3

11
240
1.56

0.278
0.109

0.22
0.0005
0.16

10
2.1
2.2

4.8
744

0.39
0.018

0.5
0.00043

14
5000

0.044

0.029
0.0002

6.0

15
40
2.1
2.1

0.0525
0.05
0.000585
0.03

0.2

40
7.4
6.8

0.006
0.027
0.0234

0.025

2.5

833
26
286

Dose
number

0.0024
0.031
0.0028
0.0028
0.008

Measured
solubility
(mg/mL)

0.5

1.5
1
0
0.5

0.5

0.5
4
0.5
10
2

0
0.5
8
7
0
20

0
0.5
0.1
0
2
2.5
0
0.1

0.5
13
0.5
5.6
9

1.5
39
1
0.5
0.5

% Excreted
unchanged
in urine

Table II. (Continued)

314.37
286.46
396.66
349.32
308.34
575.69
305.34
236.29
412.94

398.40
404.49
356.42
340.42
804.04
389.41
301.39
812.03
514.63
194.15
656.67
291.44
471.69
300.40
288.43
317.43
258.24
201.25
776.88
375.56
260.31
312.46
602.68
253.71
311.41
270.35
273.25
261.71
257.29
448.95
348.43
430.55
371.87
390.52
300.44
253.27
359.66
294.44
392.58

MW drug

2.67
5.98

2.95
4.23

3.81

1.23

2.60

5.68
7.04
1.12

1.98
2.03

6.30
0.98
2.31
3.94
6.25

4.15

4.23
1.30

3.80

3.27

0.98

5.17
2.79

0.45
1.08
2.64

0.09
2.52

0.86

0.65

4.77

3.09

3.96

0.78
0.08
0.66

Measured
LogD74

2.69
2.34

2.51

0.33
2.47

3.32

1.24
6.00
5.69

2.30
3.42

Measured
LogP

3.37

3.07
5.95

3.05
3.39

3.69
3.60
6.12
4.10

4.90
4.05
4.09

4.42

3.01

5.22
4.12
5.10
5.08
5.00

Measured
LogS molar

3.88
1.66
3.16
3.16
5.78
2.58
2.81
3.75
7.54
0.81
0.72
5.96
6.07
2.63
3.22
3.81
0.53
2.36
3.51
2.78
2.54
3.15
7.76
2.09
1.34
2.50
3.25
5.66
2.21
4.65
3.36
2.10
3.85
3.72
6.74
1.61
6.44
5.44
4.51
1.83
6.40
9.39
0.52
2.90
7.09
1.44
2.48
4.21

3.93
5.12
6.63
3.20
3.40
6.67
4.19
2.16
4.92

CLogP

3.46
3.61
4.16
4.38
7.74
4.46
3.06
3.70
4.72
1.48
5.24
4.71
5.48
3.86
3.92
2.41
2.54
3.01
3.17
1.87
2.42
4.68
6.52
2.40
3.03
2.86
3.11
3.55
2.29
6.28
1.04
1.68
4.92
4.33
4.71
2.54
5.39
2.35
4.68

minVSLgS 37.5

3
1
1
5
3
6
5
2
4

8
3
3
3
11
4
5
11
4
5
12
1
3
2
2
4
4
2
4
3
3
2
5
5
4
3
5
3
3
3
5
5
4
5
2
7
1
2
4

HBA

1
1
1
1
1
2
0
2
1

3
0
1
1
3
1
4
1
1
1
3
0
2
0
1
0
1
1
3
1
1
1
2
2
2
2
2
2
1
2
3
2
0
3
1
3
1
0
3

HBD

88.84
22.56
22.56
67.01
68.83
121.38
61.50
73.18
44.63

148.16
59.94
59.21
40.83
185.90
71.07
88.12
163.02
62.46
101.89
166.64
1.18
46.29
45.34
40.83
37.66
88.83
34.46
101.09
42.01
59.10
40.83
111.66
58.53
89.39
84.94
108.16
54.80
59.67
74.25
109.16
101.91
34.31
95.05
40.83
123.98
33.63
1.75
85.95

PSA

534
Benet, Broccatelli and Oprea

300
5
10
3
50
2
10
500
100
382
10
10
500
1000
400
1000
2000
40
50
20
50
40
50
167
50
500
20
40

Biapenem
Biotin
Bisoprolol fumarate
Bleomycin A2
Bretylium
Bumetanide
Cadralazine
Capreomycin 1B
Captopril
Carbenicillin
Carboplatin
Carteolol
Cefaclor
Cefadroxil
Cefamandole
Cefazolin
Cefepime
Cefmetazole sodium
Cefodizime
Cefonicid
Ceforanide
Cefotaxime
Cefotetan
Cefotiam
Cefoxitin
Cefsulodin
Ceftazidime
Ceftizoxime

mg
mg
mg
mg/mL
mg/mL
mg
mg
mg/mL
mg
mg
mg/mL
mg
mg
mg
mg
mg
mg
mg/mL
mg/mL
mg/mL
mg/mL
mg/mL
mg/mL
mg/mL
mg/mL
mg
mg/mL
mg/mL

mg
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg/mL
mg
Active metabolite
mg
mg/mL

8
10
4
70
12.5
12
100
250
5
1000
875
500
100
0.4
25
600
4000
40
20

10
5

mg
Active metabolite

Maximum
strength
dose unit

333

Acamprosaic acid
Acecainide; N-acetyl
procainamide
Acrivastine
Adefovir dipivoxil
Albuterol; salbutamol
Alendronate sodium
Almotriptan
Alvimopan
Amantadine
Amikacin
Amiloride
Aminocaproic acid
Amoxicillin
Ampicillin
Atenolol
Atropine (DL)
Azacitidine
Azithromycin
Azlocillin
Aztreonam
Baclofen
Benazeprilat
Bendroumethiazide
Betamipron

Generic name

Maximum
strength
dose value

Tablets
Solution (with
panipenem)
Powder
Tablets
Tablets
Solution
Solution
Tablets
Tablets
Solution
Tablets
Tablets
Solution
Tablets
Capsules
Tablets
Tablets
Powder
Powder
Solution
Solution
Solution
Solution
Solution
Solution
Solution
Solution
Powder
Solution
Solution

Capsules
Tablets
Tablets
Tablets
Tablets
Capsules
Capsules
Solution
Tablets
Tablets
Tablets
Capsules
Tablets
Tablets
Solution
Tablets
Powder
Solution
Tablets

Tablets

Formulation

(i.v.)
(i.v.)

(i.v.)

(i.v.)

Injection
Oral
Oral
Injection
Injection
Oral
Oral
Injection
Oral
Oral
Injection
Oral
Oral
Oral
Oral
Injection
Injection
Injection
Injection
Injection
Injection
Injection
Injection
Injection
Injection
Injection
Injection
Injection
(i.v.)
(i.v.)
(i.v.)
(i.v.)
(i.v.)
(i.v.)
(i.v.)
(i.v.)
(i.v.)
(i.v.)
(i.v.)
(i.v.)
(i.v.)

(i.v.)

(i.v.)

(i.v.)
(i.v.)

(i.v.)

Oral
Injection (i.v.)

Oral
Oral
Oral
Oral
Oral
Oral
Oral
Injection
Oral
Oral
Oral
Oral
Oral
Oral
Injection
Oral
Injection
Injection
Oral

Oral

Route

1000
50
5

0.0942
270

8.59
14.2
333
33

160
50
14

20
50
0.1
1.3

0.22

0.108

0.04

0.2
0.3
0.005
0.1

0.003
0.03

0.08
0.03

0.09

0.4

0.04

0.06
0.3

0.0004
0.01
1.0
0.3
0.02
0.8

0.5
0.008

0.1
50
50
333
3.5
7.8
24.8
0.002
89
39
50
10
2.1

0.05
0.1

Dose
number

0.7
0.4

50

Measured
solubility
(mg/mL)

53
43
63
68
77
45
75
90
38
82
77
60
52
93
96
80
85
80
80
99
84
30
67
80
85
60
85
93

67
45
50
45
40
2
85
98
49
65
86
88
94
57
62
6
65
68
69
18
21
98

50
81

% Excreted
unchanged
in urine

350.40
244.31
325.45
1415.58
243.17
364.42
283.33
653.70
217.29
378.41
371.26
292.38
367.81
363.39
462.51
454.51
480.57
471.54
584.67
542.57
519.56
455.47
575.62
525.63
427.46
532.55
546.58
383.41

348.45
333.24
239.32
249.10
335.47
424.54
151.25
585.61
229.63
131.18
365.41
349.41
266.34
289.38
244.21
749.00
461.50
435.44
213.67
396.45
421.42
193.20

181.21
277.37

MW drug

0.37
1.03
2.04

1.60

0.02

0.60

0.50
0.58

1.63
1.41
0.14
1.14
3.70
0.34

0.34
1.13
2.30

0.13
0.88
1.42

1.85
0.69
3.56
2.34

1.87

1.89

3.59

3.05

0.96

0.10
2.95
0.87
1.35
0.16
1.83
3.02
4.02

2.44

Measured
LogP

0.66
0.40
2.02
1.65
1.03
5.16
0.44
1.28
0.97
1.64
2.01

3.63
0.48

2.70
2.92

0.74

Measured
LogS molar

Table III. Measured and In Silico Data for 247 BDDCS Class 3 Drugs

3.80

1.89

1.70
1.20

0.46
1.76
3.40
2.40
3.14

1.98

2.10
0.45
0.32

0.23

5.07
0.96
0.07
1.99

1.25
1.60
1.52
1.61
1.03

0.69

1.11

Measured
LogD74

6.35
0.08
1.83
7.68
1.25
3.37
0.93
5.51
0.89
1.64
0.34
1.29
1.64
2.51
0.11
1.19
3.05
1.34
1.10
1.92
3.36
0.14
1.54
3.58
0.81
6.89
3.75
0.34

0.67
1.14
1.52
7.03
1.93
3.55
2.80
1.99
1.04
1.33
0.94
0.76
0.17
0.14
2.54
1.36
0.27
2.34
1.00
1.71
0.00
0.31
2.04
0.79
1.42
1.96
0.46
0.41

5
3
5
28
0
5
6
11
3
6
2
4
5
6
8
9
8
9
11
11
10
9
11
10
6
8
10
8

4
8
4
8
3
5
1
17
7
3
6
5
4
3
8
13
6
11
3
6
5
3

4
3

2.47
1.64
1.46
1.98
0.06
5.64
1.79
2.16
2.00
6.30
0.11
2.24
1.87
1.20
0.11
1.30
2.20
2.64
1.56
0.34
0.62
2.04
1.73
0.72

HBA

CLogP

2.11
1.63
0.45
4.87
1.46
1.82
2.00
5.31
1.03
2.05
0.47
0.42
0.16
0.96
0.83
3.15
2.82
1.07
0.91
0.89
3.42
1.18

0.72
0.91

minVSLgS
37.5

1
3
2
20
0
3
3
13
2
3
2
3
3
4
3
2
2
2
4
4
4
3
4
3
3
3
3
3

1
3
4
6
1
3
1
13
5
2
4
3
3
1
4
5
4
4
2
3
3
2

2
2

HBD

97.13
88.25
63.82
662.79
0.00
130.02
106.01
389.22
60.28
133.95
149.65
78.78
121.09
143.96
155.70
156.53
152.65
160.63
203.72
215.48
201.94
179.71
229.00
172.22
156.95
199.72
194.05
152.65

52.25
149.47
82.56
178.77
53.85
97.72
27.97
360.37
159.65
68.80
143.96
121.09
92.48
50.80
143.47
186.17
159.99
213.20
68.80
115.38
131.87
73.68

92.63
66.56

PSA

BDDCS Applied to Over 900 Drugs

535

40
50
200
750
2000
1000
500
10
500
75
250

2.6
800
500
125

1
0.3
5.2
250

Generic name

Ceftriaxone
Cefuroxime
Celiprolol
Cephalexin
Cephalothin sodium
Cephapirin
Cephradine
Cetirizine
Chloroquine
Cidofovir
Cilastatin

Cilazaprilat
Cimetidine
Clarithromycin
Clavulanic acid

Clofarabine
Clonidine
Cromolyn
Cycloserine
Dabigatran
Dacarbazine
Dactinomycin; actinomycin D
Dalfampridine
Daptomycin
Demeclocycline
Desmopressin
Desvenlafaxine
Dexrazoxane
Dibekacin; dideoxykanamycin B
Dicloxacillin
Didanosine
Digitoxin
Digoxin
Disopyramide
Dofetilide
Dorzolamide hydrochloride
Doxycycline
Edetate calcium disodium
Emtricitabine
Enalaprilat
Entecavir
Eptibatide
Ertapenem sodium
Erythromycin (base)
Erythromycin lactobionate
Ethambutol
Etidronic acid
Etoposide
EXP-3174
Famotidine
Ferrous sulfate

40
182

10
0.5
10
50
300
0.2
100
500
50
500
25
0.1
0.25
150
0.5
0.02
40
200
200
8
1
2
1000
500
50
400
400
50

Maximum
strength
dose value

mg/mL
mg
mg/inhalation
mg
Active metabolite
mg/mL
mg/mL
mg
mg/mL
mg
mg
mg
mg
mg/mL
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg/mL
mg
mg
mg
mg/mL
mg
mg
mg/mL
mg
mg
mg
Active metabolite
mg
mg

mg
mg
mg
mg

mg/mL
mg
mg
mg
mg
mg
mg
mg
mg
mg/mL
mg/mL

Maximum
strength
dose unit

Tablets
Capsules

Solution
Solution
Tablets
Solution
Tablets
Tablets
Tablets
Powder
Ampoules
Capsules
Tablets
Tablets
Tablets
Capsules
Capsules
Solution
Tablets
Solution
Capsules
Tablets
Tablets
Solution
Powder
Tablets
Solution
Tablets
Tablets
Capsules

Solution
Tablets
Tablets
Capsules
Powder
Powder
Capsules
Tablets
Tablets
Solution
Solution (with
imipenem)
Tablets
Tablets
Tablets
Tablets (with 875 mg
amoxicillin)
Solution
Tablets
Solution
Capsules

Formulation

(i.v.)
(i.v.)

(i.v.)
(i.v.)

(i.v.)

Oral
Oral

Injection (i.v.)
Injection (i.v.)
Oral
Injection (i.v.)
Oral
Oral
Oral
Injection (i.v.)
Injection (i.m.)
Oral
Oral
Oral
Oral
Oral
Oral
Ophthalmic
Oral
Injection (i.v.)
Oral
Oral
Oral
Injection (i.v.)
Injection (i.v.)
Oral
Injection (i.v.)
Oral
Oral
Oral

Injection (i.v.)
Oral
Topical (nasal)
Oral

Oral
Oral
Oral
Oral

Injection
Oral
Oral
Oral
Injection
Injection
Oral
Oral
Oral
Injection
Injection

Route

0.9

0.22

0.001

1.0

2.1
20

570

0.002

2.4
65

91
112

0.007

0.004
0.04
0.001
0.6

27.3
0.01
0.986
1
3.9

0.0007
0.2

0.8

0.0001
0.01

0.5
1.0

0.08
0.4
0.02

0.001
0.005
0.3
0.2

572
11

1000
1.5

4.2
0.5

210
100

6.2
2

26
0.101
100
170
25

400
200
151
12
50

Measured
solubility Dose
(mg/mL) number

55
62
50
65
85
39
10
90.3
40.5
47
47
45
42
81
60
55
30
60
55
64
10
41
95
73
60
70
50
38
5
5
79
50
38
55
67

91
62
35
43

46
96
20
91
52
48
86
50
61
90
70

% Excreted
unchanged
in urine

Table III. (Continued)

303.68
230.10
468.38
102.09
471.52
182.19
1255.45
94.12
1620.71
464.86
1069.24
263.38
268.27
451.52
470.33
236.23
764.96
780.96
339.48
441.57
324.44
444.45
292.25
247.25
348.40
277.29
831.98
475.52
733.95
1074.21
204.31
206.03
588.57
436.90
337.45
151.91

389.46
252.34
747.97
199.16

554.59
424.39
379.50
347.40
396.44
423.47
349.41
388.90
319.88
279.19
358.46

MW drug

1.50

0.60
0.64

3.43

0.57

2.79
8.86
0.60

0.43
0.28

0.06

1.24
2.83
1.26
0.43

0.21
1.60

0.24

0.83
4.80

0.33

1.10

4.30
1.91
1.14
2.40
2.20
1.15
2.10
0.31
1.54

Measured
LogD74

3.06

0.43
0.74

0.02

2.91
1.24
2.83
1.26
2.58

0.60

0.26

0.24

1.43
1.92

0.40
3.16

0.16
1.92
0.67
0.00
1.15
1.75
1.70
4.63

Measured
LogP

2.54
1.73

2.06
1.11

0.51
0.34

1.92

0.94
4.88
2.90
2.53

0.34
1.39

0.21
2.49

1.64
3.40

0.35
0.01

2.48

1.61
2.57

1.13
3.59
0.50
0.22
1.16

0.14
0.33
0.40
1.46
0.92

Measured
LogS molar

1.50
0.19
2.37
1.07
0.46
1.73
1.48
1.19
0.06
0.48
8.01
0.32
2.43
0.59
3.14
2.68
1.33
3.41
2.98
1.65
2.85
1.42
2.58
1.99
0.43
0.51
1.93
1.29
0.88
2.58
2.86
1.82
1.61
1.61
0.12
2.54
0.03
5.59
1.17
4.15

1.97
1.46
2.33
1.25
2.28
1.56
6.89
1.51
7.54
0.39
2.48
1.28
2.12
1.70
3.36
1.62
6.01
6.30
0.79
3.35
1.31
0.52
6.61
1.31
0.21
2.13
5.02
0.26
3.84
3.84
1.55
4.72
4.31
1.50
1.64
3.65

0.02
0.23
1.86
1.84
0.28
0.61
1.73
2.08
5.06
2.39
0.47

CLogP

1.01
1.91
4.00
0.31

0.31
1.76
1.73
0.28
1.72
0.27
0.07
1.42
1.17
2.99
0.77

minVSLgS
37.5

7
3
11
3
8
5
18
2
27
9
15
3
6
13
5
6
12
13
3
6
5
9
10
5
6
6
12
8
13
13
4
7
12
6
8
4

7
5
13
5

12
7
5
5
5
6
5
5
3
8
6

HBA

3
2
3
2
4
2
5
1
22
6
14
2
2
9
2
2
5
6
1
2
2
6
4
2
3
4
11
5
5
5
4
5
3
2
6
0

3
3
4
2

4
3
3
3
3
2
3
1
1
4
4

HBD

112.88
38.46
177.81
72.82
146.28
97.62
368.53
37.91
774.05
197.07
476.51
34.13
104.58
265.26
116.46
84.65
192.62
215.17
57.66
113.88
116.83
197.07
165.67
88.11
115.68
126.09
350.27
170.78
203.27
203.27
74.26
150.80
166.64
105.06
179.34
75.52

120.13
81.67
189.50
91.63

216.88
179.19
98.23
121.09
120.19
130.43
121.09
51.97
25.69
152.23
142.48

PSA

536
Benet, Broccatelli and Oprea

g/activation
mg/mL
mg
mg
mg
mg/mL
mg

g/activation

755

769

17
333
10
50
300
100
25

45

1000
5
750
300
40
600
400
2
400
10
1000
50
40
15
500
20
10
2
2000
100
100
100
1

Iopamidol

Iopromide

Ipratropium bromide
Kanamycin
Ketorolac
Lacosamide; erlosamide
Lamivudine
Latamoxef; moxalactam
Leucovorin; folinic
acid
Levalbuterol

Levetiracetam
Levocetirizine
Levooxacin
Lincomycin
Lisinopril
Lithium carbonate
Lomeoxacin
Loperamide
Loracarbef
Memantine
Metformin
Methazolamide
Methicillin
Methotrexate
Methyldopa
Methylnaltrexone
Metoclopramide
Metocurine iodide
Mezlocillin
Miglitol
Miglustat
Milnacipran
Milrinone

mg
mg
mg
mg/mL
mg
mg
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg/mL
mg
mg/mL
mg
mg
mg
mg
mg/mL

mg/mL

mg/mL

750
755

mg
mg
mg
mg/mL
mg
mg
mg/mL
mg
mg/mL
mg/mL
mg
mg
Active metabolite
mg
mg
g
mg
Active metabolite
mg
mg/mL

150
200
500
24
3000
800
25
500
40
50
2
50

50
1000
311
150

mg

180

Fexofenadine; terfenadine
carboxylate
Flecainide
Fluconazole
Flucytosine
Foscarnet
Fosfomycin tromethamine
Gabapentin
Gallium nitrate
Ganciclovir sodium
Gentamicin C1 sulfate
Gold sodium thiomalate
Guanfacine hydrochloride
Hydrochlorothiazide
Hydrodolasetron
Hydroumethiazide
Hydroxyurea
Hyoscyamine; L-atropine
Ibandronate
Imidaprilat
Imipenem
Iohexol

Tablets
Tablets
Tablets
Solution
Tablets
Tablets
Tablets
Capsules
Capsules
Tablets
Tablets
Tablets
Solution
Tablets
Tablets
Solution
Tablets
Solution
Powder
Tablets
Capsules
Tablets
Solution

Solution

Powder
Solution (equivalent
to 350 mg I per mL)
Solution (equivalent to
370 mg I per mL)
Solution (equivalent
to 370 mg I per mL)
Solution
Solution
Tablets
Tablets
Tablets
Solution
Tablets

Tablets
Tablets
Tablets
Tablets

Tablets
Capsules
Capsules
Solution
Tablets
Tablets
Solution
Capsules
Solution
Solution
Tablets
Tablets

Tablets

(i.v.)
(i.m.)

(i.v.)

(i.v.)

Topical
(aerosol)
Oral
Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Injection (i.v.)
Oral
Oral
Injection (s.c.)
Oral
Injection (i.v.)
Injection (i.v.)
Oral
Oral
Oral
Injection (i.v.)

Topical (aerosol)
Injection (i.v.)
Oral
Oral
Oral
Injection (i.v.)
Oral

Injection (i.v.)

Injection (i.v.)

Injection (i.v.)
Injection (i.v.)

Oral
Oral
Oral
Oral

Oral
Oral
Oral
Injection
Oral
Oral
Injection
Oral
Injection
Injection
Oral
Oral

Oral

1000

0.2
3

0.704
300
0.45
10

1040
0.101
50
50
97
13
1.64
1.4
41

180

200
2
70
50
500

10

0.3
50
3.56

1
0.6

6
50

50
10

48.4
1
15

0.0004

0.2

0.1
0.2

0.3

0.002
0.2
1.0
0.006
0.04

0.004
0.2
0.06

0.000001

0.0002

0.0002
0.1
0.02

0.3

0.7
0.08
0.0003

0.008
0.3

0.3

0.2
0.3

0.01
0.8
0.1

66
71
74
30
94
95
65
0.5
94
71
99
61
88
81
40
52.75
20
50
45
80
85
55
85

46

50
90
58
40
67
76
10

97

96

43
75
99
82
82
100
80
91
91
70
50
100
53
90
80
57
55
9
69
95

25

170.21
388.90
361.38
406.55
405.50
73.89
351.36
477.05
349.78
179.31
129.17
236.27
380.42
454.45
211.22
356.45
299.80
652.84
539.59
207.23
219.28
246.36
211.23

239.32

332.47
484.51
255.28
250.30
229.26
520.48
473.45

791.12

777.09

414.35
306.28
129.09
126.01
138.06
171.24
255.73
255.24
477.61
368.09
246.10
297.74
326.40
331.29
76.06
289.38
319.23
377.40
299.35
821.15

501.67

2.32

0.66

3.18
2.34

2.53
0.10
3.00
1.32

0.79
3.59
0.86
0.91
0.62
0.75
2.33
2.53
0.93

0.12

0.11
2.10
0.52
1.02
0.02

3.21

0.13
1.22
1.85
0.39
1.12
2.62

3.28

0.30

1.70
0.39
0.56
1.22

0.93
0.58

1.04

0.36
1.80
1.83

3.04
0.18
1.91

1.48

1.33
0.07

1.66

1.10

3.78
0.50

2.39
2.70

1.66
0.98

0.44
1.23

0.93
2.49
0.93

0.68

2.41
2.52
2.39
1.12
0.32

5.41

1.03
4.22

3.40

0.31
0.40

1.11

3.45
7.85

0.44

0.36

1.12
0.07

4.25
8.40

1.31

1.14
0.95
1.97
2.00

2.68

1.37

3.90

0.06
0.34
2.08
0.51
1.28
1.69
3.65
0.11
4.66
0.47
3.03
1.63
0.09
1.78
0.53
2.26
2.64
2.23
1.12
1.50
1.26
0.91
1.91
0.03

0.45
1.18
1.54
0.45
2.27
1.85
0.00
0.56
4.57
0.36
1.35
4.13
1.04
2.39
0.03
1.34
1.70
1.25
5.31
3.36
1.70
0.22
1.46
2.50

2.19
5.17
1.62
0.39
1.46
0.82
3.49

0.86

3.88

2.28
3.84
2.37
2.15
1.21
1.98
1.81

3.66
0.44
1.64
2.17
0.23
0.66
1.43
2.73
1.80
3.30
1.37
0.37
1.90
0.21
1.80
1.30
3.37
1.74
1.35
0.66

1.96

2.20
2.35
0.05
3.43
4.57
1.75
1.71
1.52
3.49
1.90
2.16
1.75
1.44
1.88
1.19
0.88
2.10
0.46
0.82
4.12

3.08

2
5
7
7
7
3
6
3
5
1
5
6
6
12
5
4
4
4
8
6
5
2
3

2
15
3
3
5
12
12

4
5
3
5
4
3
9
8
12
4
3
5
3
5
2
3
8
7
6
9

1
1
1
5
4
0
2
1
3
1
4
1
2
5
4
2
2
0
3
5
4
1
1

1
11
1
2
2
4
7

2
1
2
3
2
2
0
4
8
1
3
3
2
3
3
1
5
3
4
8

65.69
51.97
70.83
133.05
143.65
63.19
75.12
43.18
121.09
27.97
89.74
107.10
111.33
211.69
114.54
72.81
70.79
55.25
184.12
113.97
91.41
47.42
61.18

82.56

49.62
304.97
59.67
74.48
88.11
214.42
232.35

183.86

211.03

65.63
70.48
70.15
104.95
72.91
68.80
199.71
134.88
215.91
81.66
83.82
131.87
64.77
131.87
86.58
50.80
151.98
137.49
120.42
220.19

87.12

BDDCS Applied to Over 900 Drugs

537

167
0.05
15
2
25
10

250
39
(60,000
2
250
75
10
1
200

500
800
50
20
1500
1.5
80
300
1000
120

60
25

0.5

Penicillamine
Penicillin G;
benzylpenicillin
Pentostatin
Phenylethylmalonamide
Phenylpropanolamine
Pindolol
Pipecuronium bromide
Piperacillin

Piperazine
Piracetam
Pirenzepine
Plerixafor
Potassium chloride
Pramipexole
Pravastatin
Pregabalin
Procainamide
Pseudoephedrine

Pyridostigmine
Pyrimethamine
Quinaprilat

Raltitrexed
Ramiprilat
Ranitidine
Regadenoson

300
0.08

400
160
36
2.5
500
15
100
300
200
400

Mitoxantrone
Morphine 6-glucuronide
Moxioxacin hydrochloride
Nadolol
Nafcillin sodium
Naratriptan
Neomycin B sulfate
Neostigmine
Netilmicin
Nizatidine
Nystatin
Ooxacin
Olmesartan
Olopatadine hydrochloride
Oseltamivir
Oxacillin
Palonosetron hydrochloride
Pamidronate disodium
Pancuronium bromide
Pemetrexed disodium
Penciclovir

Generic name

Maximum
strength
dose value

mg
mg
Active
metabolite
mg/mL
Active metabolite
mg
mg/mL

mg
mg
mg
mg/mL
mg
mg
mg
mg
mg
mg

mg
mg/mL
units/mL)
mg/mL
mg
mg
mg
mg/mL
mg/mL

mg/mL
Active metabolite
mg
mg
mg/mL
mg
mg
mg
mg/mL
mg
mg
mg
Active metabolite
mg
Active metabolite
mg/mL
mg/mL
mg/mL
mg/mL
mg/mL
mg/g

Maximum
strength
dose unit

Tablets
Solution

Solution

Capsules
Solution (as
potassium salt)
Solution
Tablets
Tablets
Tablets
Solution
Solution (with
25 mg/mL
tazobactam)
Tablets
Tablets
Tablets
Solution
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets (discontinued;
60 mg in
combinations)
Tablets
Tablets

Solution
Solution
Solution
Solution
Solution
Cream

Tablets

Tablets
Tablets
Solution
Tablets
Tablets
Tablets
Solution
Capsules
Capsules
Tablets

Solution

Formulation

Oral
Injection (i.v.)

Injection (i.v.)

Oral
Oral

Oral
Oral
Oral
Injection (s.c.)
Oral
Oral
Oral
Oral
Oral
Oral

Injection (i.v.)
Oral
Oral
Oral
Injection (i.v.)
Injection (i.v.)

Injection (i.v.)
Injection (i.v.)
Injection (i.v.)
Injection (i.v.)
Injection (i.v.)
Topical (skin,
membranes)
Oral
Injection (i.v.)

Ophthalmic

Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Injection (i.v.)
Oral
Oral
Oral

Injection (i.v.)

Route

555
0.05

100
0.121

0.004

50
10
333.3
0.2
300
33
4

0.002

0.002
0.8

0.02
0.03
0.001
0.04
1.0

0.008

0.005

0.01

0.06
0.2
0.5

0.0003
0.3
0.0006

0.06
0.02

260

714.3

7.9

30

90
170

21.65
4
3.54

35
6.3
100

7.5
1000
27.5
30.4

Measured
solubility Dose
(mg/mL) number

50
13
30
65

85
65
96

50
70
43
70
85
90
20
90
67
43

80
79
65
54
39
71

45

64
43
65
99
46
40
46
67
80
75

7
90
22
73
27
50
40
67
85
61

% Excreted
unchanged
in urine

Table III. (Continued)

458.50
388.47
314.41
390.36

181.22
248.72
410.47

86.14
142.16
351.41
502.80
74.56
211.33
424.54
159.23
235.33
165.24

268.27
206.25
151.21
248.33
602.91
517.56

149.21
334.40

444.49
461.47
401.44
309.41
414.48
335.47
614.66
223.30
475.59
331.46
926.12
361.38
446.51
337.42
284.36
401.44
296.42
235.07
572.88
427.42
253.26

MW drug

0.25
3.89

0.26
3.31

0.85
1.70
0.65
3.02
0.15
0.68
1.77

0.48

0.14

1.50

0.95

0.68
0.17

2.23

1.18
2.36
2.01

0.98
2.05
0.35

1.77
0.34
1.20
1.01

Measured
LogS molar

0.27

2.69

0.88
1.13

0.54

1.61

0.23
1.35
1.15

1.55
0.39

1.50
1.54
0.10

2.18

3.30

4.65
0.13
2.27
0.39

3.94
1.81

0.50

2.09
0.13
0.83
1.75

1.78
1.83

1.62

7.87

1.24

0.40

0.39

2.38

1.00

0.93

0.70
0.66

Measured
LogD74

0.20

0.81

Measured
LogP

4.26
3.00
1.95
0.71
1.75
0.67
2.86

0.32
0.28
1.50
3.00

1.48
1.18
0.35
0.25
2.14
1.17
2.05
0.92
1.42
0.89

1.96
0.01
0.58
1.67
0.63
1.70

1.73
1.75

2.30
3.10
0.08
0.38
3.53
1.70
6.47
2.81
2.40
0.16
3.20
0.51
2.51
1.09
1.24
2.05
2.18
6.17
1.21
1.17
2.72

CLogP

0.13
2.91
0.50

3.10
0.45
3.12
4.68
1.07
0.66
3.75
2.11
0.52
0.80

1.17
1.61
0.99
1.40
3.57
3.44

2.60
2.21

0.60
0.23
0.83
0.39
3.46
0.72
4.21
0.51
2.52
2.55
6.39
0.57
2.31
1.06
0.57
2.86
2.72
5.20
4.27
2.23
2.17

minVSLgS
37.5

8
6
5
10

1
4
6

2
2
5
8
0
3
6
3
3
2

7
2
2
3
4
7

3
4

10
10
7
5
5
3
19
1
12
6
17
7
7
4
5
5
2
8
2
9
6

HBA

4
3
2
5

0
2
3

2
1
1
6
0
2
4
2
2
2

4
2
2
3
0
3

3
2

8
5
2
4
2
2
13
0
8
2
12
1
3
1
3
2
0
6
0
6
4

HBD

157.86
115.68
84.19
181.70

29.12
75.82
115.68

29.15
65.69
63.98
89.79
0.00
52.49
135.57
68.80
61.69
37.13

111.17
92.49
50.53
60.21
56.48
164.86

68.80
93.12

185.09
159.24
84.22
91.35
102.23
67.24
378.50
28.55
215.91
85.02
347.83
70.83
127.62
51.11
110.44
116.46
20.62
178.77
54.13
198.63
126.09

PSA

538
Benet, Broccatelli and Oprea

Temocaprilat
Temocillin disodium
Tenofovir disoproxil
Terbutaline
Tetracycline
Tetracycline hydrochloride
Ticarcillin
Tigecycline
Tiludronic acid
Tiotropium bromide
Tiroban hydrochloride
Tobramycin
Tocainide
Topiramate
Topotecan
Trimetazidine
Trimethoprim
Triptorelin
Trospium chloride
Tubocurarine
Vancomycin
Varenicline tartrate
Vecuronium bromide
Vigabatrin
Vitamin B1
(thiamine)
Zalcitabine
Zanamivir
Zoledronic acid

Risedronate
Ritodrine
Rocuronium
bromide
Rolitetracycline
Rosuvastatin calcium
Roxatidine
Saxagliptin
Sitaoxacin
Sitagliptin
Sotalol
Spectinomycin
Stavudine
Streptomycin
Sulpiride
Talinolol
Tazobactam sodium

mg
mg
Active metabolite
mg
mg
mg
mg
mg/mL
mg
mg
mg
mg
mg/mL

250
40

Active metabolite
mg/mL
mg
mg
mg/mL
mg
mg/mL
mg/mL
mg
g
mg/mL
mg/mL
mg
mg
mg
mg
mg
mg
mg
mg/mL
mg
mg
mg/mL
mg
mg

mg
mg
mg/mL

100
300
5
25
500
30
10
200
18
0.05
40
600
200
1
20
160
3.75
20
3
250
1
2
500
500

0.75
5
0.8

5
50
100
240
625
40
1000
200
100
25

mg
mg
mg/mL

150
10
10

Tablets
Powder
Solution

Solution
Tablets
Tablets
Syrup
Capsules
Solution
Solution
Tablets
Capsules
Solution
Solution
Tablets
Tablets
Capsules
Tablets
Tablets
Powder
Tablets
Solution
Capsules
Tablets
Solution
Tablets
Tablets

Tablets
Tablets
Tablets
Tablets
Solution
Capsules
Powder
Tablets
Tablets
Solution (with
200 mg/mL
piperacillin)

Tablets
Tablets

Tablets
Tablets
Solution

(i.v.)

(i.v.)

(i.m.)

(i.v.)
(i.v.)

(i.v.)
(i.v.)

(i.v.)

Oral
Topical (aerosol)
Injection (i.v.)

Injection
Oral
Oral
Oral
Oral
Injection
Injection
Oral
Oral
Injection
Injection
Oral
Oral
Oral
Oral
Oral
Injection
Oral
Injection
Oral
Oral
Injection
Oral
Oral

Oral
Oral
Oral
Oral
Injection (i.m.)
Oral
Injection (i.m.)
Oral
Oral
Injection (i.v.)

Oral
Oral

Oral
Oral
Injection (i.v.)

76.4
18

27

500
50
50
0.2

1.37

1000
10
9.8
1

13.4
213
1.7
10.9
1000
295

0.007

137
7.5
83
20
2.28
1.23
50

0.00004
0.001

0.07

0.02
0.02

0.0002

0.5

0.2
0.08
0.004

0.2

0.09
0.00009

0.002
0.2
0.4
0.3

0.001

0.0008

17.6

1250

65
100
39

82
56
58
58
77
22
60
74
65
93
38
70
40
62
70
41.7
6
63
79
92
20
60
90

29.5

55
5
57.5
24
75
78
85
70
39
55
70
52.8
77

87
10
17

211.22
332.32
272.09

448.56
414.46
519.45
225.29
444.45
480.94
384.43
569.66
318.61
392.52
440.61
467.52
192.26
339.37
421.46
266.34
290.32
1311.48
392.52
609.75
1449.29
211.27
557.84
129.16
265.36

527.58
481.55
306.40
315.42
409.82
407.32
272.37
332.36
224.22
581.58
341.43
363.50
300.29

283.12
287.36
530.80

0.44
1.27

0.99

0.11
1.09
1.46
3.02

2.33

0.33
1.28
1.54
2.62

1.59
0.02
2.42
1.64
0.42
0.29

0.30
1.65
0.43
1.46
2.18
2.47
0.78

1.25

0.37

1.30

2.16

0.91

0.76

0.90
1.30
1.30

0.57

0.14

0.24

1.64

2.60

0.83

0.83

1.41
1.41

1.25

1.15

0.79

3.21
0.89

1.24
1.76
3.16

1.25
5.56
3.07

2.56
1.52
0.80
0.48
0.91
0.91
1.28
0.83
0.26
1.71
2.00
4.72
0.26
0.04
0.73
1.18
0.98
1.22
1.16
3.55
1.14
0.90
4.33
2.22
5.97

1.22
1.32
3.71
1.54
0.66
1.17
0.83
0.07
1.64
2.34
2.92
0.94
2.05
0.91
0.04
2.25
5.29
3.50
2.82
7.43
0.28
3.70
2.68
1.58

0.47
1.90
2.35
0.11
1.25
0.69
0.23
2.88
0.49
4.26
1.11
3.15
0.65

2.62
1.65
6.40

0.82
3.71
2.62
2.48
1.33
1.70
0.11
1.31
1.60
2.10
0.99
2.27
0.42

2.80
1.42
3.53

5
10
8

6
7
10
4
9
9
6
10
6
3
6
14
2
8
6
5
7
17
2
5
24
3
3
3
4

10
8
4
4
6
4
4
9
4
19
5
4
7

8
4
0

2
8
5

3
3
1
4
6
6
3
5
4
1
3
10
2
1
2
1
2
18
1
2
19
1
0
2
2

6
3
1
2
2
1
3
5
2
14
2
4
1

5
4
0

88.11
215.70
161.62

117.18
142.75
176.07
82.87
197.07
197.07
133.95
195.34
128.24
58.42
116.61
287.82
60.51
118.72
102.76
43.06
103.14
510.46
49.62
83.96
584.97
35.06
55.30
68.80
71.29

184.85
144.83
65.68
88.67
120.37
71.38
88.93
141.47
82.44
357.04
108.62
93.35
123.90

161.04
82.87
59.59

BDDCS Applied to Over 900 Drugs

539

Acetazolamide
Acyclovir
Amisulpride
Atovaquone
Auranon
Azapropazone; apazone
Candesartan
Candesartan cilexetil
Cefdinir
Cefditoren
Cexime
Cefpodoxime
Cefprozil
Ceftibuten
Chlorothiazide
Chlorthalidone
Cinoxacin
Ciprooxacin
Clodronic acid
Cloxacillin
Dalfopristin
Daunorubicinol
Enoxacin
Eprosartan
Erythromycin stearate
Felbamate
Fleroxacin
Fosinoprilat
Furosemide
Iopanoic acid; iodopanoic acid
Lenalidomide
Levocabastine
Levonorgestrel
Medroxyprogesterone acetate
Megestrol acetate
Meropenem
Niclosamide
Nitrofurantoin
Noroxacin
Orlistat
Paliperidone
Penicillin V;
phenoxymethylpenicillin
Phenazopyridine hydrochloride
Quinupristin
Rifaximin
Roxithromycin
Sulfadiazine
Sulfamethizole
Sulsoxazole
Trandolaprilat
Triclabendazole sulfoxide
Valsartan
Vitamin B2 (riboavin)

Generic name

320
100

200
100
550
300
500
500
500

80
500
25
0.5
0.75
500
40
333.3
500
100
400
120
9
500

400
600
500
600
800

400
200
500
400
500
100
500
750
800
250
100

32
300

250
800
200
250
3
300

mg
mg/mL
mg
mg
mg
mg
mg
Active metabolite
Active metabolite
mg
mg

mg
mg
mg
mg
mg
mg
Active metabolite
mg
mg
Active metabolite
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg
mg/mL
Active metabolite
mg
mg
mg
mg
mg
Active metabolite
mg
mg
mg
mg/mL
mg
mg
mg
mg/mL
mg
mg
mg
mg
mg
mg

Tablets
Tablets

Tablets
Solution
Tablets
Tablets
Tablets
Tablets
Tablets

Tablets
Tablets
Capsules
Solution
Tablets
Tablets
Tablets
Solution
Tablets
Capsules
Tablets
Capsules
Tablets
Capsules

Tablets
Tablets
Tablets
Tablets
Tablets

Capsules
Tablets
Tablets
Capsules
Tablets
Tablets
Tablets
Tablets
Capsules
Tablets
Solution

Tablets
Capsules

Tablets
Tablets
Tablets
Tablets
Capsules
Capsules

Oral
Oral

Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Oral

Oral
Oral
Oral
Ophthalmic
Oral
Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Oral
Oral

Oral
Oral
Oral
Oral
Oral

Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Injection (i.v.)

Oral
Oral

Oral
Oral
Oral
Oral
Oral
Oral

Maximum strength Maximum strength

dose value
dose unit
Formulation Route

20
8.1
72

0.15
0.395
0.0139

0.18
0.11

0.001
0.1
0.13
0.25
0.13

7.1
3.6

2200
12
15
8.0
15

3.2
8.0

154
2.1
2.1

0.013
0.19
0.75
0.01125
0.25

2.1
91
80

133
222

0.0014
0.022
0.002

0.015
0.00045

2.7
30
6.1
3.4
3.7

36
20
3.8
1.5

0.055
0.08
0.52
0.27

0.6
0.08
0.33
0.7
0.87
0.01

29

2.6

20

1.6
1.3

0.05511

0.05

0.0615

0.64
2.5

6.5
13
75

41
3.5
0.035
12
57
86
49

47
29
1
59

90
75
50
3
60
60
52
0
15
70
41
81
73
71
92
65
60
65
80
75
4.5
25
45
30
5
45
72.5
43
66
33
66
70
52
44
60
70

213.24
1021.26
785.90
837.07
250.28
270.33
267.31
402.49
375.66
435.53
376.37

222.25
225.21
369.49
366.85
678.49
300.36
440.47
610.68
395.42
506.58
453.46
427.46
389.43
410.43
295.72
338.77
262.22
331.35
244.89
435.89
690.86
529.55
320.33
424.52
1018.40
238.25
369.35
435.50
330.75
570.94
259.27
420.53
312.46
386.54
384.52
383.47
327.13
238.16
319.34
495.75
426.50
350.40

3.38
3.53

1.46

2.75
0.09
0.54
1.01

2.09

4.58
3.15

5.90
3.92
3.28
3.03
3.31

0.47
1.03

2.03

0.24

1.00
1.11
0.87

2.52
1.54

0.19
2.00

3.60

0.69
1.54

0.29

2.15

2.48

0.20

1.82

0.28

3.82

0.45
1.76

1.10
0.85
1.55
1.21

4.40
3.10
2.63

5.35
4.24
5.28

4.58
5.76

2.73
3.72
3.49
2.53
2.63
4.64

3.34
2.79
4.50

3.85
3.71
2.75
3.10

3.92

0.24
0.85

1.78

3.69
4.09

0.26
1.56
1.10

2.54
1.95

0.98
2.42
1.80
6.35
3.79
1.79
5.43
7.33
0.48
1.46
0.25
0.41
1.87
1.21
1.00
0.45
1.74
0.73
0.14
2.52
0.92
1.36
1.60
4.80
1.61
0.50
0.33
4.85
1.90
4.70
0.53
1.86
3.31
4.01
3.58
3.28
4.34
0.47
0.78
8.61
1.12
1.94
2.05
7.05
7.24
2.29
0.10
0.42
0.22
2.31
4.36
4.86
0.73

0.77
2.68
1.30
5.06
1.91
3.35
2.11
4.35
0.27
6.73
0.91
0.09
0.49
1.68
1.59
2.98
2.05
0.45
4.95
2.98
5.35
1.12
0.07
4.18
3.84
1.93
0.27
4.22
2.38
4.31
2.64
2.60
4.34
4.69
4.57
0.11
4.10
1.74
0.32
7.63
2.77
2.34
2.37
6.15
7.16
4.95
1.93
1.90
2.01
0.72
4.52
4.77
2.64

5
12
12
16
5
5
4
6
1
6
9

5
6
6
3
5
4
7
8
8
9
10
9
6
8
6
4
7
6
6
5
9
11
7
5
13
2
6
5
5
3
4
4
2
3
3
6
4
5
6
3
5
5

2
4
5
5
2
2
2
3
1
2
5

2
3
2
1
0
0
2
1
4
2
4
3
4
4
2
3
1
2
4
2
2
6
2
2
5
2
1
2
3
2
2
1
1
0
0
3
2
1
2
1
1
2

88.00
236.20
205.94
224.19
99.95
102.86
102.81
115.68
52.01
113.69
161.81

121.43
112.32
107.55
59.10
117.05
52.35
114.16
136.25
166.41
162.89
193.48
155.91
143.96
171.87
126.91
120.90
91.03
75.12
128.24
116.46
177.78
204.62
85.36
92.48
203.27
110.07
61.72
101.70
130.02
68.50
88.83
60.70
40.83
63.61
63.61
116.86
99.56
118.74
75.12
86.97
76.16
102.23

Measured solubility
% Excreted
Measured
Measured Measured minVSLgS
(mg/mL)
Dose number unchanged in urine MW drug LogS molar LogP
LogD74
37.5
CLogP HBA HBD PSA

Table IV. Measured and In Silico Data for 53 BDDCS Class 4 Drugs

540
Benet, Broccatelli and Oprea

27.97
126.97
27.97
84.94
126.97
27.97
21.80
14.57
14.57
23.37
117.30
1
0
1
2
0
1
0
1
1
1
4
1
10
1
3
10
1
2
1
1
2
5
1.74
3.50
2.85
2.35
3.50
1.74
1.62
2.83
1.89
1.67
1.76
1.50
1.85

1.54
1.08
1.76

2.13
0.50
0.10
0.83
1.85
0.28

0.40
0.13
2.60
2.27
2.10

1.25
7.00
0.41
2.66
7.56
1.29
0.69
1.77
0.99
0.20
0.92
1.54
1.76
0.65

0.5

0.06
0.006
0.00005
0.00002

2.2

1
63.7
212
1000
2.5
333

541
the lowest solubility under the conditions listed above. The
solubility criteria over the pH range 17.5 can create marked
differences from compilation to compilation for drugs that are
salts. For example, one may nd in the package insert for
atazanavir sulfate that the drug is slightly soluble in water
(45 mg/mL, free base equivalent) with the pH of a saturated
solution in water being about 1.9. Reporting this solubility
would lead to the assignment of atazanavir sulfate as a class 1
drug in BCS and BDDCS. However, it is known that
atazanavir, as for almost all the protease inhibitors, exhibits
very poor solubility in solutions at pH above 5.5, although
these solubilities are not reported. Therefore, we list atazanavir sulfate as a class 2 drug and no specic solubility is
listed in Table II. Another example of a basic drug is imatinib
mesylate (and other kinase inhibitors) where the package
insert states Imatinib mesylate is soluble in aqueous
buffers pH 5.5 [a published value of 200 mg/mL can be
found] but is very slightly soluble to insoluble in neutral/
alkaline aqueous buffers. Therefore, we list this drug in
Table II as class 2 with a solubility of 1 mg/mL, determined
at pH 7.4. Similar variances can occur for acidic drugs
where solubility may be very low at pH 1. This concern
that the pH range maybe too restrictive has been
addressed (34) and explicated (35) previously for acidic
drugs. Individual references are not given for the solubility
values because in many cases the values in the tables are
the authors consensus view of the appropriate value based
on a number of experimental results as discussed above.
This is a technique followed by Dr. Benet when he rst
introduced the table of pharmacokinetic parameters in
Goodman and Gilman and represents a decision of the
two senior authors alone in reviewing all of the literature
data that they could nd. A single solubility value is given
in the ve tables in milligrams per milliliter.
Figure 3 depicts a box plot of the measured solubility
values (representing about 68% of drugs listed in Tables I, II,
III, and IV) used for assigning BDDCS classication. Class 2
and 4 drugs are less soluble than class 1 and 3 drugs, but there

mg
mg/mL
mg
mg
mg/mL
mg
mg
mg
mg
mg
mg
Amphetamine sulfate
Atracurium
Chlorphentermine
Chlorpropamide
Cisatracurium besylate
Dextroamphetamine
Diethylcarbamazine citrate
Mecamylamine
Methamphetamine
Phenmetrazine
Vitamin C; ascorbic acid

10
10
25
250
10
15
100
2.5
5
25
1000

Tablets
Solution
Tablets
Tablets
Solution
Tablets
Tablets
Tablets
Tablets
Tablets
Capsules

Oral
Injection (i.v.)
Oral
Oral
Injection (i.v.)
Oral
Oral
Oral
Oral
Oral
Oral

0.01

0.001
30

40
8.5
17
20
8.5
40
35
50
40
19
25

135.21
929.17
183.68
276.74
929.17
135.21
199.30
167.30
149.24
177.25
176.13

Measured
LogP
Measured
LogS molar
MW drug
% Excreted
unchanged in urine
Dose number
Measured solubility
(mg/mL)
Route
Formulation
Maximum strength
dose unit
Maximum strength
dose value
Generic name

Table V. Measured and In Silico Data for 11 BDDCS Class 0 Drugs

Measured
LogD74

minVSLgS
37.5

CLogP

HBA

HBD

PSA

BDDCS Applied to Over 900 Drugs

Fig. 3. Box plot of Log10 measured molar solubility values used for
the BDDCS classication against BDDCS categories. Arrows pointing left show the mean, arrows pointing right the median; the shaded
area indicates the 95% condence interval, while the box itself is the
interquartile range; the horizontal bars indicate the minimum and
maximum values; squares are outliers. Class 1, 1.79 1.27 (266
drugs); class 2, 4.29 1.12 (167); class 3, 1.38 1.18 (159); class
4, 3.70 0.96 (35)

542
is a considerable overlap since the highest dose strength also
affects the assignment. Further analysis with respect to the
in silico predicted solubility values is addressed below.
Percent Excreted Unchanged in the Urine (%Urine)
Although the FDA (4) and EMA (9) guidances list 90%
and 85% absorption, respectively, as a cutoff for high
permeability, Wu and Benet (1) believed that a 70% cutoff
for BDDCS would be sufcient since the purpose of BDDCS
was not to provide a regulatory exemption but rather to make
a prediction of drug disposition. As noted above, Wu and
Benet (1) found that there were very few drugs in which the
percent of dose metabolized fell between 30% and 70%. One
may be tempted to use the percent urine values in the tables
to test this hypothesis, but this would be incorrect since a
number of class 3 and class 4 drugs are known to be excreted
unchanged in the bile, as are the metabolites of some class 2
and possibly class 1 drugs, depending on the BDDCS class of
the metabolite. When a drug is given intravenously, the
percent of drug unchanged in the urine is readily obtained.
When for a given drug only the oral dosage forms are
available, frequently limited human data may be available on
a parenteral experimental formulation. In these two previous
cases, that is the value listed in Tables I, II, III, and IV. Where
only oral human data are available, the authors used their
best judgment in correcting the value with a bioavailability
parameter. Lowering the cutoff to 70% obviates in most cases
any error that would be inherent in classication based on
this assumption. However, the criterion for poor metabolism
in BDDCS is excretion of unchanged drug both in the urine
and in the bile. The extent of biliary excretion of unchanged
drug is an experimentally difcult value to obtain in humans
for most drugs. But this is the criterion that we have used in
the assignment of BDDCS classication for the more than
900 drugs listed in the tables. It will be obvious in reviewing
Tables III and IV that a number of class 3 and class 4
compounds show very low values for %Urine. For example,
erythromycin is listed in Table III with 4% excreted
unchanged in the urine; however, only 15% of an erythromycin dose is metabolized with more than 80% excreted
unchanged in the bile. Thus, for the class 1 and 2 drugs in
Tables I and II, the low percent urine does reect fairly
accurately the degree of metabolism since for these
compounds it is usually the metabolites that are excreted
into the bile, not the parent drug. However, for the class 3
and the class 4 compounds, the assignment was not made
based only on the percent urine data value in Tables III
and IV. The box plot depicted in Fig. 4 reects these
differences between classes 1 and 2 versus classes 3 and 4,
with the very wide standard deviations below the mean for
classes 3 and 4 reecting the importance of biliary
excretion in these assignments.
As mentioned earlier, Benet et al. (2) proposed that
90% metabolism could be an additional criterion that
regulatory agencies may use in conrming that a drug was
more than 90% absorbed. In that paper, Benet et al. (2)
restricted the metabolic processes to those that would only
occur following absorption such as cytochrome P450
metabolism or metabolism by phase II enzymes found in
the gut or the liver. However, in the present compilation,

Benet, Broccatelli and Oprea

the metabolism criterion for BDDCS assignment does not
limit the metabolic processes to these enzymes only. In the
present tables, when a drug is metabolized 70% or more, it
is classied as highly metabolized and if the metabolism is
<70% is categorized as poorly metabolized (readers will
note in Fig. 4 that ve class 1 and 2 drugs show between
>30% and 40% excreted unchanged. For these compounds, it is the authors belief that these drugs operate
more like the assignment made).
Maximum Strength Dose
For US-approved drugs, the maximum dose strength is
taken from the package insert. In a number of cases, we have
included drugs in the tables that have been removed from the
market and drug products where a package insert was not
available. In those cases, the maximum strength dose was
selected based on an evaluation of literature data.
Figure 5 is a box plot of the Log10 of the maximum
strength dose (molar) against BDDCS. It appears that class 4
drugs have the highest dose (molar) compared with other
BDDCS classes, whereas class 1 drugs have the lowest strength.
This most likely relates to differences in bioavailability, but
may also relate to differences in efcacy. The more
lipophilic highly metabolized drugs tend to be more active
toward wanted and off targets because of a higher
capability of nonspecic interactions. Therefore, it is more
likely that drugs that are less lipophilic and less metabolized are given at a higher dose since they are probably less
potent and since there is less risk of toxicity.
BDDCS Classification and Dose Number
High versus low solubility was determined using the
FDA/EMA criteria of the maximum strength dose of the drug
at its lowest solubility over the pH range of 17.5 being
soluble in 250 mL of water at 37C. The solubility cutoff may
be expressed as the dose number, which is calculated as the
highest dose strength (milligrams) divided by 250 mL and the
lowest solubility (milligrams per milliliter). When the dose
number is 1.0, the drug is considered to have high solubility;
when the dose number is >1.0, the drug is considered to have
low solubility. Using the solubility (dose number) and the

Fig. 4. Box plot of%Urine against BDDCS. Key: as in Fig. 3. Class 1,

5.36.8 (302); class 2, 3.56.3 (228); class 3, 61.324.4 (243); class 4,
47.827.1 (50)

BDDCS Applied to Over 900 Drugs

Fig. 5. Box plot of the Log10 of the maximum strength dose

(molar) against BDDCS. Key: as in Fig. 3. Class 1, 4.121.01 (288);
class 2, 3.790.98 (237); class 3, 3.671.13 (163); class 4, 3.240.69
(43)

percent metabolism criteria discussed above, the BDDCS

class was assigned. For non-orally dosed drugs and active
metabolites, no dose number is given in the tables, and the
BDDCS assignment is based on the best estimate of the
relevant solubility as determined by the authors. This opens
the possibility of a more rened system, the dose-dependent
BDDCS, dBDDCS. Such a system, based on evaluating
multiple strength doses, could highlight class migration,
which is likely to occur for some drugs, versus class
propensity. We anticipate that some drugs will migrate to a
neighboring class depending on dose strength, whereas most
drugs, however, are likely to show preference for one class
only. By migrating existing class 4 drugs toward class 3 or
class 2 drugs toward class 1, one is likely to obtain improved
biopharmaceutical characteristics; thus, FDA approval for
novel formulations can be requested using a drug repurposing
mechanism (36) under Section 505(b) (2) of the Federal
Food, Drugs and Cosmetic Act.
Class Zero
For a number of drugs, such as amphetamine, changes in
urinary pH affect the extent of metabolism. Therefore, it is
not possible to assign a BDDCS class. It appears for the 11
drugs listed in Table V that they all are predominantly highly
soluble in water and thus would probably be BCS class 1
drugs, or BDDCS class 1 or class 3 depending upon urine pH.

543
LogP and measured LogD at pH 7.4 when such values are
available. Again, individual references for the values are not
included. However, in the section below, we will comment on
prediction differences and accuracy with respect to in silico
calculations. Figure 6 is a box plot of the measured LogD
values at pH 7.4 against BDDCS assignment.
This provides some partial explanation for the food
effects mentioned earlier. BDDCS class 2 drugs have high-fat
solubility, as illustrated by their higher measured LogD7.4
(Fig. 6), compared with other classes. Under high-fat meal
conditions, higher amounts of drug are therefore likely to be
solubilized in the intestinal contents and become available to
the enterocytes for (passive) absorption. However, we do not
see a similar effect for the more hydrophilic, poorly soluble
class 4 drugs. Since BDDCS class 1 drugs already are
solubilized, they would receive no benet from increased
lipid solubilization.
IN SILICO PARAMETERS
As discussed above, BDDCS assignments were based
on the measured parameters of extent of metabolism and
solubility, although in the latter case, for extremely poorly
soluble and very highly soluble compounds, a numerical
value is not always available. However, it is also useful to
analyze how well or how poorly in silico parameters can
predict the BDDCS classication and to use this type of
computation to make other predictions. Thus, for each
compound in the tables, we also include: the molecular
weight of the listed compound; the calculated LogP
(CLogP) using the method of Leo (40); the number of
hydrogen bond donors (HDo) for the active moiety; the
number of hydrogen bond acceptors (HAc) for the active
moiety; the polar surface area (PSA) calculated using the
method of Clark (41); and the log of the lowest water
solubility calculated over the pH range 37.5 (minVSLgS;
VolSurf+), as proposed by Cruciani et al. (42,43). We also
calculated (and list in Supporting Info) the solubility of
each drug in its neutral form using Tetkos solubility in
water (TLogSw) prediction using ALOGPS 2.1 [see (44)].
We hope that this parameter compilation and discussion
will be valuable to investigators trying to develop better
prediction methods.

MLogP and MLogD7.4

When no active transport processes are involved, pharmaceutical scientists expect lipid/water partition coefcients
to be correlated with drug permeability. The Lipinski Rule of
Five (3739) was an attempt to dene the upper limits of
lipophilicity for developing NMEs that are likely to be orally
available. As noted above, Takagi et al. (3) evaluated the
correlation of measured LogP and calculated LogP with BCS
high versus low human jejunal permeability rate compounds,
nding that the correlation only held about two thirds of the
time. Since there is interest in these parameters and following
our guideline of attempting to use measured experimental
values when available in making predictions, we have
included in Tables I, II, III, IV, and V values for measured

Fig. 6. Box plot of MLogD7.4 values against BDDCS. MLogD7.4 for

class 2, 2.091.91 (121) is the highest among all classes. Class 1, 1.25
1.68 (219); class 3, 1.262.19 (110); and class 4 0.421.77 (20).
Key: as in Fig. 3

544

Benet, Broccatelli and Oprea

Fig. 8. In silico parameters for 698 orally dosed drugs. For each,
calculated property average value and standard deviation are shown.
PSAD (polar surface area density) = MW/PSA

Fig. 7. Probability of extensive metabolism in different measured

LogP and CLogP ranges. The plot show the probability of being
extensively metabolized in a specic LogP (CLogP) range if a set
with equal number of extensively and poorly metabolized drugs is
considered

Solubility and Dose Number

Both in silico solubility predictions correlate poorly
with the measured values, although the VolSurf+ correlation (r2 = 0.33) is somewhat better than the ALOGPS
solubility (r 2 = 0.24). However, even with these poor
correlations, the predicted dose numbers (cDose
Number) with the calculated VolSurf+ solubility were
reasonable for class 1, 2, and 3 drugs. Results for the
VolSurf+ (and ALOGPS) solubilities were as follows:
Class 1 drugs are classied with an accuracy of 78.6%
(54.3%), class 2 with an accuracy of 76.9% (84.3%), and
class 3 with accuracy of 89.4% (65.7%). The predictive
accuracy for class 4 drugs was very poor (39.5%) for the
VolSurf+ prediction, but reasonable when the pH effect is
not considered (79.1% when using ALOGPS). Upon
further examination, 17 of these drugs are well predicted
by cDose Number. These 17 drugs have a class2-like
CLogP prole (average CLogP = 3.76). The deviation
between measured LogS and minVSLgS is on average
0.66 for these drugs. For the 26 class 4 drugs that are
poorly predicted, the average CLogP is 0.27, and the
average measured LogP is 0.11. The deviation between
measured LogS and minVSLgS is on average around 3.00.
A number of these 26 drugs are likely to exist as zwitterions at
pH below 7.5; several among them are uoroquinolone
antibiotics. In particular, for enoxacin, ciprooxacin,
noroxacin, and cinoxacin, solubility prediction based on
melting point and LogD failed, probably due to self-

association (45). In support of this hypothesis, Ross and Riley

(45) noted that the solubility of these drugs at the same pH
increases with temperature. The lowest measured solubility data
for class 4 drugs are observed when these molecules behave as
zwitterions (pH 7). Therefore, the reason for class 4 assignment
prediction error is likely to relate to self-association for drugs
that behave as zwitterions. This is less likely to play a role in the
digestive tract since varying pH conditions, the presence of
counterions, and surfactants (e.g., bile acids) might diminish the
importance of self-association. Despite the relatively high
success of the ALOGPS method for class 4, solubility
predictions for these zwitterions in neutral form, which
essentially ignores the pH effect, should be used with caution.
Partition Coefficient and Extent of Metabolism
As discussed above, a high extent of metabolism is
expected for high LogP compounds and vice versa. In
contrast to the predicted versus measured solubility values
discussed above, the correlation between MLogP versus
CLogP is quite good (r2 =0.83). Thus, it might be expected
that both MLogP and CLogP would reasonably well predict

Fig. 9. BDDCS distribution of 698 marketed, immediate release,

orally dosed drugs in the present table versus the predicted
distribution of small molecule NMEs being developed by the industry

BDDCS Applied to Over 900 Drugs

class 1 and 2 drugs versus class 3 and 4 drugs, with the results
shown in Fig. 7. For either measured or calculated LogP>2,
the probability of extensive metabolism is 80.1% and 79.3%,
respectively. For LogP values<0, the probability of poor
metabolism is 83.5% for MLogP and 83.9% for CLogP.
However, when LogP values range from 0 to 2 (31.7% of
drugs for MLogP and 27.5% of drugs for CLogP), the
probability assignments are not very good, with MLogP
doing somewhat better for extensively metabolized drugs
and CLogP doing somewhat better for poorly metabolized
drugs (Fig. 7). As with solubility predictions, the poorest
probability of extent of metabolism was found for class 4
drugs (data not shown).
Summary of In Silico Parameters for Orally Dosed Drugs
Figure 8 highlights the in silico parameters for 698
orally dosed drugs. As expected, CLogP is higher and PSA
lower for extensively metabolized (class 1 and 2) drugs.
However, an unexpected nding is the very marked
similarity for solubility and (somewhat less) for CLogP
predictions for class 1 and 4 drugs. This reects the
inherent confounding aspects of the dose number calculation used in both BDDCS and BCS, as discussed earlier
in this manuscript and by Rinaki et al. (46), and the
generally poor predictability for class 4 drugs. We also
calculated the polar surface area density (PSAD = MW/
PSA) and are struck by the empirical observation of the
similarity and low coefcient of variation for PSAD
(Fig. 8) for the class 3 and class 4 poorly metabolized
drugs. As noted by the arrows in Fig. 8, class 2 and class 3
drugs exhibit the extremes for the in silico measures of
solubility and partition coefcient.
OTHER COMMENTS
The listing of drugs in the ve tables is essentially
inclusive of small molecules only as most peptide and protein
drugs were not included in the compilation. However, there
are exceptions, such as the inclusion of exenatide and
liraglutide. We note that all the drugs listed in the 2011
Goodman and Gilman compilation (47) are included in the
present table except, for streptokinase and interferon alpha
and beta. Since many drugs on the market are in fact prodrugs, when data were available, our listing includes the
parameters for some of the better characterized active
metabolites, even when the metabolite itself was not a
commercially available product and thus the maximum
strength dose does not exist. For example, see urazepam
and desalkylurazepam (both Table I) as well as losartan
(Table II) and EXP3174 (Table III). In those cases, the
BDDCS classication was made based on the dose of the
parent drug, the known fraction conversion to the active
species, and the solubility of the active metabolite. The
nding of Wu and Benet (1) that very few drugs fall in the
3070% metabolism range does not mean that there are no
such drugs. For example, in Table III, moxioxacin HCl has
been shown to be metabolized 52% (14% as a glucuronide
and 38% as a sulfate conjugate) while 45% is excreted
unchanged (25% in the feces and 20% in the urine). Similarly,
palonosetron HCl (Table III) is excreted 40% unchanged and

545
50% via CYP enzymes, while phenazopyridine (Table IV) is
excreted 41% unchanged and 49% metabolized.
WHERE CAN ADDITIONAL INFORMATION BE
FOUND?
Oprea and co-workers (48,49) have indexed the
information for over 1,260 drugs in WOMBAT-PK, a
database that includes pharmacokinetic parameters (such
as those indexed in GoodmanGilman), physicochemical
properties, and target bioactivities (see http://www.sunset
molecular.com/index.php?option=com_content&view=
article&id=16&Itemid=11). WOMBAT-PK contains additional information related to the BDDCS entries described
in the tables. However, all pertinent data used to categorize
individual drugs for the BDDCS classication are provided here.
Further information about drugs can also be found in public
resources as follows: Chemical information, physicochemical
properties, and bioactivities are compiled in PubChem (http://
pubchem.ncbi.nlm.nih.gov/), ChEMBL (https://www.ebi.ac.uk/
chembl/), and ChemSpider (http://www.chemspider.com/).
Detailed drug information can be retrieved at DailyMed (http://
dailymed.nlm.nih.gov/dailymed/about.cfm), DrugBank (http://
drugbank.ca/), and European Medicines Agency (http://www.
ema.europa.eu/).
Information as found in the ve tables, together with the
physicochemical properties and target bioactivities, can serve as
a source for investigating and predicting the characteristics of
NMEs in drug development. However, we add a further caution
concerning in silico methodologies that may be developed based
on our compilation of data for drugs on the market at some time.
This is illustrated in Fig. 9 where we have compiled the BDDCS
classication of the orally dosed drugs in our tables. In Fig. 9, we
compare this distribution of commercially available drugs with
our predictions of the distribution of total NMEs that have at
some time been dosed to humans, particularly in the last decade.
Based on our prior evaluation of high-activity medicinal
chemistry compounds (50), we estimate that of the drug
candidates being investigated by the industry, up to 70% are
large molecular weight, lipophilic, poorly soluble class 2
compounds, another 20% are not only poorly soluble but also
poorly permeable class 4 compounds, while only 10% are
high-soluble class 1 and class 3 compounds. Thus, when in
silico methodologies are developed and tested on commercially available drugs, it is important to remember that
40% of drugs are BDDCS class 1, and as predicted in
Fig. 2, these compounds will not exhibit disposition
characteristics affected by transporters in the gut and liver,
whereas up to 95% of NMEs are likely to be affected.
Therefore, in testing such new methodologies, it is critical
that both the training and test compound sets have a
strong representation of compounds other than BDDCS
class 1.
ACKNOWLEDGMENTS
The authors were supported in part in preparation of the
ve tables and this manuscript by NIH grants GM-61390, GM75900 and GM-90457 (LZB), and by GM-095952, MH-084690,
and CA-118100 (TIO). We thank Molecular Discovery Ltd. and
Professor Cruciani for the VolSurf+ suite license.

546
Supporting Info Available An excel le is available as supporting
info containing the following data for the 927 drugs dataset: name,
BDDCS class, max dose strength value, max dose strength unit,
formulation, route, measured solubility, dose number, % excreted
unchanged in urine, MW drug, MW solution, pDose, measured LogS
molar, measured LogP, measured LogD7.4, ALOGPS 2.1 solubility,
cDose Number (ALOGPS based), minVSLgS, cDose Number
(minVSLgS based), cLogP, HBA,HBD, PSA, and violations to Rules
of Five. Denitions for the terms used only in the supporting info le
may be found at the end of that data set. In addition, box plots of
minVSLgS, ALOGPS 2.1 solubility, MLogP, cLogP, MW, PSA
parameters against BDDCS are provided.

REFERENCES
1. Wu C-Y, Benet LZ. Predicting drug disposition via application of
BCS: transport/absorption/elimination interplay and development of a biopharmaceutics drug disposition classication
system. Pharm Res. 2005;22:1123.
2. Benet LZ, Amidon GL, Barends DM, Lennerns H, Polli JE,
Shah VP, et al. The use of BDDCS in classifying the permeability
of marketed drugs. Pharm Res. 2008;25:4838.
3. Takagi T, Ramachandran C, Bermejo M, Yamashita S, Yu LX,
Amidon GL. A provisional biopharmaceutical classication of
the top 200 oral drug products in the United States, Great
Britain, Spain and Japan. Mol Pharmaceut. 2006;3:63143.
4. Food and Drug Administration. Guidance for industry: waiver of
in vivo bioavailability and bioequivalence studies for immediaterelease solid oral dosage forms based on a biopharmaceutics
classication system. Food and Drug Administration, Rockville,
MD. 2000. www.fda.gov/cder/guidance/index.htm.
5. Amidon GL, Lennerns H, Shah VP, Crison JR. A theoretical
basis for a biopharmaceutics drug classication: the correlation
of in vitro drug product dissolution and in vivo bioavailability.
Pharm Res. 1995;12:41320.
6. Benet LZ, Larregieu CA. The FDA should eliminate the
ambiguities in the current BCS biowaiver guidance and make
public the drugs for which BCS biowaivers have been granted.
Clin Pharmacol Ther. 2010;88:4057.
7. Chen ML, Amidon GL, Benet LZ, Lennerns H, Yu LX.
The BCS, BDDCS and regulatory guidances. Pharm Res.
2011;28:17748.
8. Lennerns H. Intestinal permeability and its relevance for
absorption and elimination. Xenobiotica. 2007;37:101551.
9. European Medicines Agency. Guideline on the investigation of
bioequivalence. Doc. Ref.:CPMP/EWP/QWP/1401/98 Rev.1/Corr.
http://www.ema.europa.eu/pdfs/human/qwp/140198enrev1n.pdf.
Accessed 28 March 2010.
10. Chen ML, Yu L. The use of drug metabolism for prediction of
intestinal permeability. Mol Pharmaceut. 2009;6:7481.
11. Fraga S, Pinho MJ, Soares-da-Silva P. Expression of LAT1 and
LAT2 amino acid transporters in human and rat intestinal
epithelial cells. Amino Acids. 2005;29:22933.
12. Lyrica package insert. http://dailymed.nlm.nih.gov/dailymed/
drugInfo.cfm?id=42134#nlm34090-1.
13. Shugarts S, Benet LZ. The role of transporters in the pharmacokinetics of orally administered drugs. Pharm Res. 2009;26:203954.
14. Matthews EJ, Krulak NL, Benz RD, Contrera JF. Assessment of
the health effects of chemicals in humans: I. QSAR estimation of
the maximum recommended therapeutic dose (MRTD) and no
effect level (NOEL) of organic chemicals based on clinical trial
data. Curr Drug Discov Technol. 2004;1:6176.
15. Benet LZ. The drug transporter-metabolism alliance: uncovering
and dening the interplay. Mol Pharmaceut. 2009;6:163143.
16. Benet LZ. Predicting drug disposition via application of a
biopharmaceutics drug disposition classication system. Basic
Clin Pharmacol Toxicol. 2010;106:1627.
17. Benet LZ, Cummins CL, Wu C-Y. Transporter-enzyme interactions: implications for predicting drugdrug interactions from
in vitro data. Curr Drug Metab. 2003;4:3938.

Benet, Broccatelli and Oprea

18. Fleischer D, Li C, Zhou Y, Pao LH, Karim A. Drug, meal and
formulation interactions inuencing drug absorption after oral
administration, clinical implications. Clin Pharmacokinet.
1999;36:23354.
19. Custodio JM, Wu C-Y, Benet LZ. Predicting drug disposition,
absorption/elimination/transporter interplay and the role of food
on drug absorption. Adv Drug Deliv Rev. 2008;60:71733.
20. Wu C-Y, Benet LZ. Disposition of tacrolimus in isolated
perfused rat liver: inuence of troleandomycin, cyclosporine,
and GG918. Drug Metab Dispos. 2003;31:12925.
21. Lau Y, Huang Y, Frassetto L, Benet LZ. Effect of OATP1B
transporter inhibition on the pharmacokinetics of atorvastatin in
healthy volunteers. Clin Pharmacol Ther. 2007;81:194204.
22. Zheng HX, Huang Y, Frassetto Y, Benet LZ. Elucidating
rifampins inducing and inhibiting effects on glyburide pharmacokinetics and blood glucose in healthy volunteers: unmasking
the differential effects of enzyme induction and transporter
inhibition for a drug and its primary metabolite. Clin Pharmacol
Ther. 2009;85:7885.
23. Lau YY, Okochi H, Huang Y, Benet LZ. Multiple transporters
affect the disposition of atorvastatin and its two active hydroxy
metabolites: application of in vitro and ex situ systems. J
Pharmacol Exp Ther. 2006;316:76271.
24. Lau YY, Okochi H, Huang Y, Benet LZ. Pharmacokinetics of
atorvastatin and its hydroxy metabolites in rats and the effects of
concomitant rifampicin single doses: relevance of rst-pass effect
from hepatic uptake transporters, and intestinal and hepatic
metabolism. Drug Metab Dispos. 2006;34:117581.
25. Frymoyer A, Shugarts S, Browne M, Wu AH, Frassetto L, Benet
LZ. Effect of single-dose rifampin on the pharmacokinetics of
warfarin in healthy volunteers. Clin Pharmacol Ther. 2010;88:5407.
26. Sussman NL, Waltershied M, Butler T, Cali JJ, Riss T, Kelly JH.
The predictive nature of high throughput toxicity screening using
a human hepatocyte cell line. Cell Notes. 2002;3:710.
27. Wadelius M, Sorlin K, Wallerman O, Karlsson J, Yue Q-Y,
Magnusson PKE, et al. Warfarin sensitivity related to CYP2C9,
CYP3A5, ABCB1 (MDR1) and other factors. Pharmacogenomics
J. 2004;4:408.
28. Oprea TI, Tropsha A, Faulon J-L, Rintoul MD. Systems
chemical biology. Nature Chem Biol. 2007;3:44750.
29. Oprea TI, May EE, Leito A, Tropsha A. Computational
systems chemical biology. Meth Mol Biol. 2011;672:45988.
30. Khandelwal A, Bahadduri PM, Chang C, Polli JE, Swaan PW,
Ekins S. Computational models to assign biopharmaceutics drug
disposition classication from molecular structure. Pharm Res.
2007;24:224962.
31. Willmann S, Schmitt W, Keldenich J, Lippert J, Dressman JB. A
physiological model for the estimation of the fraction dose
absorbed in humans. J Med Chem. 2004;47:402231.
32. Zhao YH, Le J, Abraham MH, Hersey A, Edershaw PJ,
Luscombe CN, et al. Evaluation of human intestinal absorption
data and subsequent derivation of a quantitative structure
activity relationship (QSAR) with the Abraham descriptors. J
Pharm Sci. 2001;90:74984.
33. Meylan MW, Howard PH, Boethling RS. Improved method for
estimating water solubility from octanol water partition coefcient.
Environ Toxicol Chem. 1996;15:1006.
34. Yazdanian M, Briggs K, Jankovsky C, Hawi A. The high
solubility denition of the current FDA Guidance on Biopharmaceutical Classication System may be too strict for acidic
drugs. Pharm Res. 2004;21:2939.
35. Rinaki E, Dokoumetzidis A, Valsami G, Macheras P. Identication
of biowaivers among class II drugs: theoretical justication and
practical examples. Pharm Res. 2004;21:156772.
36. Oprea TI, Nielsen SK, Ursu O, Yang JJ, Taboureau O, Mathias
SL, et al. Associating drugs, targets and clinical outcomes into an
integrated network affords a new platform for computer-aided
drug repurposing. Mol Inf. 2011;30:10011.
37. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental
and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv
Rev. 2001;46:326.
38. Lipinski CA. Drug-like properties and the causes of poor
solubility and poor permeability. J Pharmacol Toxicol Methods.
2000;44:23549.

BDDCS Applied to Over 900 Drugs

39. Lipinski CA. Chris Lipinski discusses life and chemistry after the
Rule of Five. Drug Discov Today. 2003;8:126.
40. Leo AJ. Calculating log Poct from structures. Chem Rev.
1993;93:1281306.
41. Clark DE. Rapid calculation of polar molecular surface area
and its application to the prediction of transport phenomena.
1. Prediction of intestinal absorption. J Pharm Sci.
1999;88:80714.
42. Cruciani G, Crivori P, Carrupt P-A, Testa B. Molecular elds in
quantitative structurepermeation relationships: the VolSurf
approach. TheoChem-J Mol Struc. 2000;503:1730.
43. The VolSurf + program, version 1.0.4 is distributed by Molecular
Discovery Ltd. http://www.moldiscovery.com.
44. Tetko IV. Computing chemistry on the web. Drug Discov Today.
2005;10:1497500.
45. Ross DL, Riley CM. Aqueous solubilities of some variously
substituted quinolone antimicrobials. Int J Pharmaceutics.
1990;63:23750.

547
46. Rinaki E, Valsami G, Macheras P. Quantitative biopharmaceutics
classication system: the central role of dose/solubility ratio. Pharm
Res. 2003;20:191725.
47. Thummel KE, Shen DD, Isoherranen N. Design and optimization of dosage regimens: pharmacokinetic data. In: Brunton L,
Chabner B, Knollman B, editors. Goodman and Gilmans the
pharmacological basis of therapeutics, vol. 12th. New York:
McGraw-Hill; 2011. p. 1891990 (Appendix II).
48. Olah M, Rad R, Ostopovici L, Bora A, Hadaruga N, Hadaruga D,
et al. WOMBAT and WOMBAT-PK: bioactivity databases for lead
and drug discovery. In: Schreiber SL, Kapoor TM, Wess G, editors.
Chemical biology: from small molecules to systems biology and
drug design. Weinheim: Wiley-VCH; 2007. p. 76086.
49. Tetko IV, Oprea TI. Early ADME/T predictions: toy or tool? In:
Varnek A, Tropsha A, editors. Chemoinformatics: an approach to
virtual screening. London: Royal Society of Chemistry; 2008. p. 24067.
50. Oprea TI. Current trends in lead discovery: are we looking at the
appropriate properties? J Comput Aided Mol Design. 2002;16:32534.