Comparative pharmacokinetic changes and drug therapy in an older population.

The aging process--physiologic, pathophysiologic and sociogenic--increases the variability of patient reactions to drug therapy, even within the same patient. This variability in the elderly patient may cause drug toxicity or subtherapeutic levels, particularly of drugs with narrow therapeutic indexes. An analysis of age-related changes in pharmacokinetics, essential to proper geriatric care, examines the absorption, distribution, metabolism, and elimination of drugs. Delayed gastric emptying slows drug absorption, because most drugs are absorbed in the small intestine. The rise in gastric pH with age will affect drugs whose absorption is pH-dependent. Changes in total body water and the ratio of lean to fatty tissue affect drug distribution; thus, the lipophilicity of a drug must be considered. Drug metabolism is altered chiefly because of changes in the oxidative microsomal enzymes of the liver. Reduced hepatic blood flow also contributes to a decrease in hepatic clearance. Notably, cimetidine seems to inhibit the oxidative metabolism of drugs by the liver. In the case of some drugs, metabolism begins with enzymes of the intestinal mucosa. Declining renal function, a reduction in both renal blood flow and glomerular filtration rate, is a major contributor to drug toxicity in the elderly. Methods for using serum creatinine to determine renal function are discussed. Guidelines and procedures for the clinical monitoring of drug "overdose" in the elderly are presented.