Pharmacokinetic Assessment of the Effect of Age on the Disposition and Pharmacologic Activity of Drugs

Abstract

Aging is associated with a number of physiologic changes. These include decreases in plasma albumin concentration, lean body mass and total body water, cardiac output, renal function (glomerular filtration and renal tubular secretion), and activity of drug metabolizing enzyme systems (reviewed in refs. 1–3). Superimposed upon these age-related changes, and difficult if not impossible to distinguish from these in a clinical setting, are the cumulative effects of environment (including smoking, medications, and diet) and disease. It is not surprising, therefore, that there is evidence suggesting age-dependent changes in the absorption, distribution, metabolism, and excretion of drugs. Such changes may be expected to result in corresponding modifications in the intensity and duration of pharmacologic effects but age may also affect the intrinsic response of receptor sites to drugs. Since the pertinent literature on pharmacokinetics related to advanced age has been reviewed thoroughly in several recent publications (1–3), the purpose of this presentation will be to focus on the pharmacokinetic principles that must be considered in the design, analysis, and interpretation of studies of the effect of age on the disposition and pharmacologic activity of drugs.