ABSTRACT
Over recent decades a revolution in analytical methodology has led to a better understanding of the processes of drug absorption, distribution, metabolism, and elimination, allowing pharmacokinetics to emerge as a distinct discipline. The justification for an increased interest in pharmacokinetics is presumably based upon the premise that a drug will be used more appropriately when its behavior in the body is better understood. It certainly would appear self-evident that a drug’s action must be somehow related to its presence in the body: thus, factors which increase drug clearance or which prevent a medicine from gaining access to the body are likely to be associated with reduced efficacy; factors which lead to drug accumulation may result in exaggerated effects or toxicity. Applying the principles of classical pharmacology, the action of a drug can be envisaged as the biochemical or physiological consequence of its interaction with tissue receptors. There are, in fact, relatively few clinical circumstances in which the therapeutic effect of a drug can be explained quite so precisely, but there is evidence of increasing success with receptor-directed drug development. Although the possibility exists for irreversible “hit and run” effects, when activity can continue after a drug is no longer detectable in the circulation, most drug-receptor interactions appear to be reversible processes allowing an equilibrium to be established between drug at the receptor site and drug in the rest of the body, including “accessible” sites such as the bloodstream. In such circumstances it ought to be possible to characterize the relationship between blood level and effect and use plasma levels to control drug therapy. For any individual medicine it is a mistake to assume that a clear relationship exists in the absence of supportive data.
