(a)Plasma
concentrationTime Time0Concentration
in the excreted
urine0(b)Figure 8.2 Typical variations in the concentration of a drug with time in samples of (a) plasma
and (b) urine after the administration of a single oral dose of the drug at time zero. In both cases
the precise shape of the graph will depend on the drug being studied
The process of elimination means that it is important to have a method of
monitoring the concentration of a drug in contact with its site of action. Since
the precise site of action is often unknown the concentration of the drug is
usually monitored by following the concentration of the drug in the plasma and
other suitable body fluids (Figure 8.2). These measurements are statistically
correlated with the effects of the drug on humans and, where this data is difficult
to obtain, animals. However, the results of these animal experiments have been
extrapolated to humans with varying degrees of success.
8.1.1 General classification of pharmacokinetic properties
The pharmacokinetic properties (ADME, see section 2.7.1) of a drug are speci-
fied in terms of measurable parameters such as plasma concentration, biological
half-life and rate constants. The methods used to calculate these parameters are
independent of the method of administration, although the values obtained will
depend on the administrative route (see section 2.6). For example, intravascular
routes will not normally give values for absorption parameters. However,
intravascular routes do give higher concentrations of the drug in the general
circulatory system (systemic circulatory system).
8.2 Pharmacokinetics and drug design
A study of the pharmacokinetic properties of a compound indicates which
properties need to be modified in order to produce a more effective analogue.
Consider, for example, a drug that is not suitable for development because it has
too short a duration of action. The logical way forward is to determine the likely
structural cause of this rapid elimination and then test analogues that either do
160 PHARMACOKINETICS