Pharmacokinetic factors influencing variability in human drug response.

It is well recognised that the clinical response to drug administration varies widely between individuals and that most of this variability is pharmacokinetic in origin. In general, variability arises because of inter-individual differences in rates of drug absorption, drug distribution and elimination, either by metabolism or excretion. Variability of drug response is also a consequence of a variety of drug interactions which may influence pharmacokinetic parameters. Among the many factors which are responsible for the variation in human drug response, age is relatively important. As a consequence of impaired metabolism and excretion the inter-individual variation in the kinetic of many drugs is much greater in the elderly. Also the degree of plasma-protein binding, in turn, influences the distribution, action, metabolism and renal excretion of drugs. Thus changes in plasma protein binding of drugs, e.g. in diseased states, may give rise to altered pharmacokinetic and possibly altered drug response. The above factors influencing variability in drug response are discussed with particular reference to examples of non-steroidal antiinflammatory drugs used in the treatment of rheumatic diseases.