Age and the Metabolism of Drugs

Abstract

Many factors contribute to the altered responsiveness of the elderly to drug therapy [1]. Of these, particular attention has been given to investigating the effect of age upon the rate of drug elimination since, unless appropriate reductions in dosage are made, significant age-related reductions in clearance will tend to lead to higher blood levels, and hence a greater risk of toxicity [2]. The effects of age on renal drug clearance are now well-documented [3-5], and parallel the decline in renal function which occurs in the elderly. Physicians are thus accustomed to matching the dosages of drugs which undergo renal excretion to elderly patients' renal function. In many instances, serum creatinine levels alone provide sufficient guide to appropriate doses although, for drugs with low therapeutic ratio, it may be necessary to measure plasma drug levels to avoid toxicity. Age-related changes in the rates of drug metabolism have also been reported for many common therapeutic agents. Unfortunately, no clear pattern has emerged, and those changes that do occur are superimposed on .the wide range of genetic and environmental factors known to influence rates of drug metabolism. Two general trends have emerged: first, and with some notable exceptions, drugs undergoing hepatic microsomal oxidation are likely to be metabolised more slowly in the elderly, whilst those that are conjugated are usually uninfluenced by age; second, drugs with high hepatic clearances and extraction ratios (such as chlormethiazole and labetalol), and which undergo extensive 'first-pass', metabolism during oral absorption, may show substantially increased bioavailability in the elderly [2].