Pharmacokinetic Problems Solved

1) Following the administration of a 250 mg

intravenous bolus dose of a drug, the drugplasma concentration immediately after injection
was found to be 17 mcg/mL. Calculate the
apparent volume of distribution.
Answer:
Volume of distribution = Dose/C0(conc. at time 0)
= 250/17
= 14.7 L
Note: 1mcg/ml = 1mg/L
2) A patient received a 300 mg dose of an
antibiotic by intravenous bolus injection at 6
A.M. At 10 A.M. the concentration of drug in the
body was 2.4 mcg/mL. If the apparent volume of
distribution of this drug is known to be 37 L,
calculate the amount of drug in the body at 10
A.M.
Answer:
Amount of drug in body = Vd x plasma conc. at that
time
= 37 x 2.4
= 88.8 mg

3) A 75-kg male patient was given a 60 mg dose

of a drug by intravenous bolus injection at 9 A.M.
At 3 P.M. the concentration of drug in the body
was found to be 0.28 mcg/mL. If the volume of
distribution of this drug is known to be 0.22 L/kg,
calculate the amount of drug in the body at 3
P.M.
Answer:
Vd= 0.22 L/kg
For 75kg male Vd= 0.22x75 = 16.5 L
Amount of drug in the body at 3 P.M = Vd x plasma
conc. at that time
= 16.5 x 0.28
= 4.62 mg
4) The minimum effective concentration of
diazepam has been reported to be 300 ng/mL. If
the apparent volume of distribution of diazepam
in a patient is 90 L, calculate the size of dose
that must be given to produce a plasma
concentration of 300 ng/mL.
Answer:
Note: 1ng/ml = 10-3mg/L
Desired plasma conc. = 300 ng/ml = 0.3 mg/L
Loading dose = Vd x desired plasma conc.
= 90 x 0.3
= 27 mg

5) The volume of distribution of Fluoxetine is

3000 liters. Calculate
The amount of drug in the body (in mg)
when plasma concentration is 3 ng/ml
The plasma concentration (in ng/ml)
when the amount of drug in the body is
30 mg.
Answer:
Note: 1ng/ml = 10-3mg/L
Plasma concentration = 3 ng/ml = 0.003mg/L
Amount of drug in body = Vd x plasma conc. at that
time
= 3000 x 0.003
=9
Plasma concentration (in ng/ml) when the amount of
drug in the body is 30 mg = Amount of drug in body/ Vd
= 30/ 3000
= 0.01 mg/L
= 0.01 x 1000 ng/ml
= 10 ng/ml
(Note: 1ng/ml = 10-3mg/L so 1mg/L = 1000 ng/ml

6) The pharmacokinetic parameters of a drug for

a 60 kg man are as follows:
Target plasma concentration: 10 mg/L
Volume of distribution: 0.6 L/Kg
Bioavailability: 60%
Calculate the loading dose
Answer:
Vd = 0.6 L/kg for 60kg man it will be 0.6 x 60 = 36L
Loading dose = Vd x desired plasma conc.
= 36 x 10
= 360mg
Now bioavailability = 60%
Therefore its 60mg in 100mg, then for 360mg it will be
= (100 x 360)/60 = 600mg
Loading dose = 600mg
7) An antiarrhythmic drug has a desirable
concentration of 200g/L. Its volume of
distribution is 0.70 L/kg. What bolus i.v. dose
should be administered to the patient weighing
60 kg?
Answer:

Vd = 0.70L/kg for 60kg man it will be = 0.70 x 60 = 42L

Bolos Loading dose = Vd x desired plasma conc.
= 42 x 200 mcg
= 42 x 0.2
= 8.4 mg
(Note: 1mcg = 10-3mg therefore 200mcg = 0.2mg)
8) The area under the plasma concentration
versus time curve following the intravenous
administration of a single 500 mg bolus dose of a
drug as an aqueous solution was found to be 285
mcg-hr/mL, and the area under the plasma
concentration versus time curve from a similar
dose administered orally as a tablet was found to
be 265 mcg-hr/mL. what is the extent of
absorption from the tablet formulation?
Answer:
Bioavailability = AUC(oral)/ AUC(IV)
= 265/285
= 0.92
= 92%
Extent of absorption from the tablet formulation = 500
x 0.92
= 464.9mg

9) Calculate area under the plasma concentration

versus time curve from 0-14 hours from the
following data obtained following the
administration of a single 500 mg dose of an
antibiotic. If MEC is 7.2 mcg/mL, calculate the
onset, intensity, and duration of action
TIME (hr)

CONC (mg/L)

TIME (hr)

CONC (mg/L.)

1 (T1)

5.8 (C1)

8 (T8)

10.0 (C8)

2 (T2)

9.2 (C2)

10 (T10)

8.5 (C10)

4 (T4)

12.0 (C4)

12 (T12)

7.1 (C12)

6 (T6)

11.5 (C6)

14 (T14)

6.0 (C14)

C1 T1

5.8

(C1 + C2) (T2 - T1)

15

(C2+C4 ) (T4 - T2)

42.4

(C4+C6) (T6 - T4)

47

(C6+C8 ) (T8 - T6)

43

(C8+C10 ) (T10 - T8)

37

(C10+C12 ) (T12 - T10)

31.2

(C12+C14 ) (T14 - T12)

26.2

Total

247.6

Answer:
AUC (total 0 to ) = AUC (0 - 14) + AUC (14 - )
AUC (0 - 14) = C1 x T1 + [(C1+C2)(T2-T1)] + [(C2+C4)
(T4-T2)] + [(C4+C6)(T6-T4)] + [(C8+C10)(T10-T8)] +
[(C10+C12)(T12-T10)] + [(C12+C14)(T14-T12)]
= 123.8
last concentration

AUC (14 - ) =

Kel
log (C10, T10) log

Kel() = (C12, T12)

Time
duration

Kel = log(8.5) log(7.1)/2

= 0.09
AUC (14 - ) =

last concentration
Kel

= 6/0.09 = 66.66

AUC(total 0 to ) = AUC (0 - 14) + AUC (14 - )

= 123.8 + 66.66
= 190.4 hr/ L

For onset make a graph for given concentration vs time

14
12
10
8
Conc (mg/ltr)

12 11.5
9.2

10

6 5.8
4
2
0
Time (hr)

8.5
7.1
6
Conc

As MEC is 7.2 = so by drawing a line horizontal from

conc vs time curve at conc 7.2 we get onset of action in
1.4 hr (duration is till 12 hr)
for duration of action = 12 hr 1.4 = 10.6 hr
intensity = maximum concentration = 12 mg/ L

10) Following data is obtained for 2 formulations

of an antimicrobial agent in volunteers of
average weight 50 kg.
Drug Product

Dose (mg/kg)

AUC (g.hr/l)

Oral Tablet

745

Oral Capsule

955

What is the relative bioavailability of tablet

against capsule?
AUC (tablet)

Relative bioavailability of tablet against capsule =

AUC
(capsule)

= 745/955
= 0.78
= 78%

11) Following data is obtained for 3 formulations

of Drug A in volunteers of average weight 50 kg.
Drug Product

Dose (mg/kg)

AUC (g.hr/l)

i.v. solution

1.2

450

Oral capsule

4.0

736

Oral Tablet

827

What is the absolute bioavailability of the

drug from capsule?
What is the relative bioavailability of capsule
against tablet?
Absolute BA of drug from capsule=AUC (Capsule)/
AUC (IV)
But doses are different, so take AUC for same dose
AUC (CAP)=736/4=184

AUC (IV)=450/1.2=375
Absolute BA=184/375
=0.49
=49%
Relative BA of capsule against tablet=AUC
(CAP)/AUC (TAB)
=736/827
=0.888
=89%

12) A drug has a volume of distribution of 175

liters and its clearance is 0.49 L/min. Calculate
its half-life in units of hours.
Answer:
Clearance = Vd x Kel (elimination rate constant)
Clearance = 0.49 L/min
= 0.49 x 60 L/hr
= 29.4
Kel = clearance/Vd
Kel = 29.4 / 175
= 0.168/hr
T1/2 = 0.693/Kel
= 0.693/0.168
= 4.125 hr
= 4.125 x 60 min

= 247.5 min

13) Drug A follows first order kinetics. After 4

t, 56.25 mg of drug A has been eliminated.
What will be the concentration of drug A
present in the body after 4 t?
Answer:
Note: if 100mg drug is given
1 t1/2
50mg
2 t1/2
25mg
eliminated in

Total 93.75mg drug is

3 t1/2

12.5mg
4 t1/2
6.25mg

4 t1/2.

Therefore, if Total 93.75mg drug is eliminated in 4

t1/2.from 100mg then 56.25mg drug eliminated in 4 t1/2
= (100 x 56.25)/93.75
= 60mg
concentration of drug A present in the body after 4 t
= 60mg 56.25mg
= 3.75mg

14) A newer cephalosporin is given by

intravenous route and it has exclusive renal
elimination. The normal maintenance dose is
240mg/day. What will be the dose rate (mg/hr) of
this drug if patients creatinine clearance is half
normal to maintain desired concentration?
Answer:
Dose in renal insufficiency = Normal dose X Patients
creatinine level
normal creatinine level
here patients creatinine clearance is half normal
therefore
the dose rate (mg/hr) of this drug = 240 x
= 120 mg/24hr
= 5mg/hr

Note:
Formula for creatinine clearance = 140 Age(years) x
Weight (kg)
72 x Serum
creatinine (mg/dl)
= for female
multiply by 0.85

15) A 72 year old 60 kg male is to be

administered aminophylline by continuous
intravenous infusion. The desired steady-state
concentration of amoniphylline in this patient is
16 mg/l. If apparent volume of distribution of
aminophylline in this patient is 35 L and K =
0.1155/hr, and the patient receives a loading
dose to attain the desired steady-state
concentration at the start of infusion, calculate
the maintenance dose (infusion rate) needed to
maintain the desired steady-state concentration
during continuous infusion.
Answer:
Loading dose = Vd x desired plasma conc.
= 35 x 16

= 560mg
Maintenance dose = loading dose x Kel
= 560 x 0.1155
= 64.68mg/hr

16) A 42 year old 70 kg male is to be

administered aminophylline by continuous
intravenous infusion. The desired steady-state
concentration in this patient is 16 mg/L. The
apparent volume of distribution of the drug is 30
L, the rate constant of elimination is 0.086625/hr,
and this patient receives a loading dose to attain
the desired steady-state concentration at the
start of infusion, calculate the rate of infusion
needed to maintain the desired steady-state
concentration during continuous infusion.
Answer:

Loading dose = volume of distribution x steady state

concentration
= 30L x 16mg/L
= 480 mg
Maintenance dose = loading dose x elimination t
= 480mg x 0.086625/hr
= 41.58mg /hr

17) A drug has a clearance of 12.6 ml/min and a

volume of distribution of 12 liters. Calculate its
elimination rate constant in units of h-1.
Answer:
Clearance = 12.6ml/min
Converted to L / h
Clearance = 12.6 x 60 hr/ 1000 L
= 126 x 6/1000
= 0.756 L/hr

Clearance = volume of distribution x Kel(elimination

constant)
Kel = clearance / volume of distribution
Kel = 0.756/12
= 0.063 /h
18) A drug has elimination rate constant of 0.012
h-1. Calculate its elimination half-life.
Answer:
t = 0.693/Kel(elimination constant)
= 0.693/ 0.012 h-1
= 57.75 hr