Fundamentals of Medicinal Chemistry

drug’s chemical nature and the physical conditions at the site of absorption.

However, most drugs exhibit approximately first order absorption and elimin-

ation kinetics except when there is a high local concentration that saturates the

absorptive and/or elimination mechanisms, in which case zero order character-

istics are often found.

The rate of change of the amount (A) of an orally administered drug in the body

with time will depend on the relative rates of absorption and elimination, that is:

dA=dt¼rate of absorptionrate of elimination (8:29)

The changes in a drug’s plasma concentration with time may be calculated for

a specific pharmacokinetic model by substituting of the appropriate rate expres-

sions into Equation (8.29). For example, for a one compartment model in which

the drug exhibits first order absorption and elimination (Figure 8.10), it is

possible to show that:

Cp¼

FD 0

Vd

kab

(kabkel)

(e

kelt

e

kabt

)(8:30)

wherekabandkelare the absorption and elimination rate constants respectively

andD 0 is the dose administered. The value ofkabmay be obtained by substitut-

ing the relevant values forF,D 0 ,Vd,kel, andtin Equation (8.30).

kab kel

(a)

Vd

First order

absorption

First order

elimination

Cp

Timet

(b)

Figure 8.10 (a) A one compartment model for a single orally administered dose. (b) The plasma

concentration–time curve for a drug that exhibits first order kinetics for both its absorption and

elimination

Expressions similar to Equation (8.30) may be obtained for drugs that do not

exhibit first order absorption and elimination characteristics by substituting the

appropriate kinetic relationships in Equation (8.29). For example, for a drug

that exhibits zero order absorption and first order elimination kinetics, Equa-

tion (8.29) becomes:

dA=dt¼k 0 kelA (8:31)

EXTRAVASCULAR ADMINISTRATION 175