Fundamentals of Medicinal Chemistry

8 Pharmacokinetics

8.1 Introduction to pharmacokinetics

The action of a drug is initially dependent on it reaching its site of action in

sufficient concentration for a long enough period of time for a significant

pharmacological response to occur. The concentration range over which the

drug is effective is referred to as its therapeutic window (see section 2.6). The

relationship of this concentration to the dose administered is not simple (Figure

8.2). Once a drug is absorbed into the body it must find its way to its site of

action. In the course of this transportation some of the drug will be metabolized

(see Chapter 9) and some will be irreversibly excreted by the liver and/or kidneys

and/or lungs. Theirreversible processes by which a drug is prevented from

reaching its site of action are collectively referred to aselimination. However,

uptake into the tissues is not regarded as an elimination process since it is

usually reversible, the drug returning to the general circulation system (systemic

circulation) in the course of time (Figure 8.1).

Administration

Tissue Distribution

Absorption

Site of action

Metabolism

plus

Excretion

Elimination

Effect

Intravascular

route

Extravascular

route

Figure 8.1 The general stages and their relationships in the life cycle of a drug after

administration

Fundamentals of Medicinal Chemistry, Edited by Gareth Thomas
#2003 John Wiley & Sons, Ltd
ISBN 0 470 84306 3 (Hbk), ISBN 0 470 84307 1 (pbk)