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Encyclopedia of Physical Science and Technology EN011J-559 July 25, 2001 18:57

806 Pharmacokinetics

FIGURE 1 Pharmacokinetics versus pharmacodynamics. Pharmacokinetics deals with the phases of drug absorp-
tion, drug distribution, and drug elimination. Pharmacodynamics defines the biological effect of a drug at a site of
action.

The practical use of the mathematical approaches of phar- Here C 0 is the concentration in the body compartment
macokinetics requires data consisting of measurements of (typically equal to plasma concentration in a human or
the rate of drug entry into the organism, time-dependent animal subject) at time zero, t is the time, and the drug
drug concentration in specific compartments within the elimination rate constant k elim can be found from the half-
organism, and the rate of drug removal from the organ- life or from the negative slope of the terminal phase of
ism. Since the largest amount of data is available for the semilog curve, as illustrated in Fig. 3. The definition
mammals—in particular, humans—mammalian systems
will be emphasized in this article. Figure 2 illustrates a
more detailed conceptual model of pharmacokinetic pro-
cesses in humans. Each of these processes will be dis-
cussed in turn and specific mathematical approaches will
be given. For more detailed approaches, the reader is re-
ferred to the Bibliography at the end of the chapter.

I. BASIC PHARMACOKINETIC CONCEPTS

The following basic terminology is used in pharmacoki-
netics: half-life, volume of distribution, bioavailability,
and mechanisms of transport.

A. Half-Life
The half-life (t 1/2 ) of a drug is equal to the time required
for its concentration to decrease by one half. Many drugs FIGURE 3 Semilogarithmic plot of plasma concentration of a
drug versus time in a one-compartment system. The initial part of
follow “first-order” kinetics and, as illustrated in Fig. 3,
the curve depends on the route of administration. The half-life of a
give a straight line on a semilog plot. This can be mathe- drug equals the time required for the plasma concentration to de-
matically described by the following equation: crease by 50%. The drug elimination rate k elim can be found from
the terminal slope of the curve. The concentration in the plasma
0.693
C = C 0 exp(−k elim t), where k elim = . (1) at time zero C 0 is found by extrapolating the plasma concentration
t 1/2 curve back to x = 0.