The influence of some disease states on drug disposition

The course of action of a drug is dependent upon the normal functioning of a number of organs which combine to absorb, distribute, metabolise and excrete the drug at a characteristic rate. A pathological condition of any of these organs may disturb not only their individual contribution to the course of the drug action, but as a secondary effect, those of other organs. Numerous studies of the effect of diseases of the cardiovascular system, gastrointestinal tract, liver and kidney have shown that organ dysfunction may be reflected in a changed rate and/or extent of absorption, apparent volume of distribution, plasma protein binding, plasma half-life and plasma and hepatic clearance. Moreover, from a clinical point of view, an important observation has been that for a given pathology, the pharmacokinetic consequence is not necessarily the same for all drugs. At the present time it is not always possible to predict the effect of a given disease on the effectiveness of therapy or to correlate changed kinetics with conventional organ function tests. In some disease states there is a strong argument for the monitoring of each individual patient's plasma drug level especially in the case of drugs with a low therapeutic index. It is also evident that further carefully controlled pharmacokinetic studies need to be carried out to elucidate the underlying mechanisms responsible for observed changes in kinetic constants. A greater understanding of the nature of these mechanisms may eventually help in the design and development of new drugs and in the more effective use of existing ones.