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Pharmacokinetics
Objective is to model the time course of the drug in plasma. One
way to do this is through compartmental analysis.
Compartments:
 systems that are continuous and nonhomogeneous are replaced
with compartments that are discrete and in which concentrations,
and so on, are homogeneous.
tissue, lymph
intravenous
drug in
dosage form
oral
liver
blood plasma
bound  free
site of
action
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excretion
metabolism
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Open one-compartment model
 process of distribution to each compartment is much faster
than absorption into blood and elimination
 drug concentration everywhere in the compartment is equal
(CSTR)
 elimination processes are pseudo-1st order
Vd
ka
D
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Cp
DB
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kel
Example
A proprietary drug in clinical trials is injected in human volunteers in
order to determine the elimination constant which was 0.02 min-1.
The company wants to use this information to develop a tablet
formulation which must have a Tmax of 20 minutes. Find the
absorption rate constant that the drug must have, assuming that all
the drug is absorbed and the initial mass of drug in the tablet is 580
mg. If the volume of distribution of the drug is 58 L, calculate the
the zero order release rate required from a controlled release
device that achieves the same Cmax as achieved with the tablet.
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Bioavailability
absolute bioavailability
 any drug delivered extravascularly has the potential of being bound

or eliminated before reaching bloodstream
amount of drug reaching bloodstream is equal to the area under the
Cp vs t curve, AUC
absolute bioavailability =
AUC extra
AUC IV
relative bioavailability
 some drugs cannot be given by iv
 bioavailability determined by comparison to standard dosage form
relative bioavailability =
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AUC test
AUC s tandard
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Therapeutic Index
no. of individuals
 not all individuals respond in same manner
minimum dose for response
(mg/kg)
therapeutic index (TI)
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TD50
TI 
ED50
Bioequivalence
 comparison of amounts of same drug that are absorbed from 2
different formulations of the same dosage form (generics)
 the two formulations are considered equivalent if there is no
significant difference between any of Cmax, Tmax, AUC
Cp
time
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