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Introduction to pharmacokinetics
Pharmacokinetic models
One-compartment open model
Multicompartmental models
Pharmacokinetic model of oral absorption
Drug Distribution and protein binding
Student presentation & Discussion
Introduction
Various routes of administration
Eye
Nasal
Ear
Oral
Sublingual
Buccal
Intramuscular
Subcutaneous
Intravenous
Intrasynovial
Intracardiac
Intrathecal
Rectal
Vaginal
Urethral
Topical
Dose of drug
administered
Biopharmaceutics
ABSORPTION
Drug conc. in
systemic circulation
DISTRIBUTION
Drug in tissues
Of distribution
Pharmacokinetics
ELIMINATION
Drug conc
at site of action
Drug metabolized
Or excreted
Pharmacologic effect
Pharmacodynamics
Clinical response
Toxicity
Efficacy
Drug conc-response
relationship
MTC
MEC
ADME Processes
Absorption
Distribution
Metabolism
Excretion
Drug Disposition
Pharmacokinetic
model
Compartment models :
Mammillary model
Catenary model
Physiologic model
Mammillary model
Multicompartment model
Assumptions
The drug would be transferred to other
compartments (k12, k21, k13, k31)
The transferred lasted when equilibrium is
reached, at this point the change in drug
conc in central comp will be equal to that in
other comps
Equation for Cp vs t curve is a summation
of several equation of first order kinetics
Diagram of a two
compartment model
Parameters
One open compartment model
k0 or ka, kel, t1/2, C, X, Vd app
Multi compartment model
k0 or ka, kel, t1/2, C, X, Vd app, and k12,
k21, k13, k31
Equations
The change of the amount of drug in the
body according to 1st order kin:
X X 0e
k el t
k el t
logX logX 0
2.303
Vd app
X = Vd x C
Vd = a proportionality constant that relate
X and C
C
C C0e
k el t
k el .t
logC logC0
2.303
Vd apparent
Has no physiologic meaning
For some drugs, Vd app exceed the
total body water (60 L)
V (L/kg)
V (L/70 kg)
Sulfisoxazole
0.16
11.2
Phenytoin
0.63
44.1
Phenobarbital
0.55
38.5
2.4
168
490
Diazepam
Digoxin
t1
0.693
k el
kel , hr-1
t1/2 el, hr
Acetaminophen
Diazepam
Digoxin
Gentamicin
Lidocaine
Theophylline
0.28
0.021
0.017
0.35
0.43
0.063
2.5
33
40
2.1
1.6
11
Plot of ln C vs t
dose
V
C0
Example calculations:
After an iv dose of 500 mg, V=30 L, kel = 0.2/hr. Calculate Cp at
2 & 4 hr.
Using eq.
And
then
dose
dose k el t
C C 0 e k el t
V
Cp
e
C0
V
C0p = 500/30 = 16.7 mg/L
Cp2hr = 11.2 mg/L
Cp4hr = 7.5 mg/L
Clearance
dX u /dt
Cl r
C
Renal Clearance
Systemic Clearance
Cl r k el Vd app
X0
Cls Vk el
AUC
Vd app
Vd app
X0
k el AUC
Vdapp
X0
k el AUC
AUC
Dose
AUC
V k el
Intravenous infusion
Model:
A semilog plot of Cp vs t
for iv infusion
Cp vs t profile for iv
infusion with a loading dose
k0
Vd app k el
1 e
k el t
Css
k0
Vd app k el
C Css 1 e k el t
Css C k el t
log
Css
2.303
A semilog plot of (Css-C)/Css vs time yields a straight line
with a slope of kel/2.303, then kel can be calculated.
Application of equations
C
10
1 e
k0
k el t
Vd app k el
60
1 e 0.17t
0.17 25
then,
0.708 = 1-e-0.17*t, thus 0.292 = e-0.17*t
therefore -0.17*t = -1.231 or t = 7.24 hr
C at post infusion
Kel can also be calculated from data collecting after stopping
the infusion
k t'
logC logC max el
2,303
or
k0
k el t'
k el T
logC log
1 e
Vd k el
2.303
Calculation of Vd by using
Css and AUC data
k0
Vd
Css k el
k 0T
Vd
k el AUC
Loading dose
X0 = Css * Vd
The amount of drug in the body after
simultaneous an iv loading dose and
initiation of constant rate iv infusion:
X X 0e
k el t
k0
k el t
1 e
k el