DRUG DISPOSITION AND HEPATOTOXICITY IN THE ELDERLY

Overall, the aged liver seems to function remarkably well in the elderly. Decreased drug disposition is selective and modest and there is no compelling evidence of greater susceptibility to drug-induced or other types of injury. Drug-drug interactions and concurrent derangements accompanying advanced age may, however, contribute to adverse drug effects. Still, the aged, consume about three times as many therapeutic agents as other people. Most of these are metabolized in the liver before excretion. With increasing age, hepatic blood flow falls and so does hepatic volume. Moreover, binding of some agents normally carried on albumin may decrease. In contrast, increasing age has relatively modest effects on hepatic drug metabolism and these are highly selective. In the healthy aged, hepatic drug elimination is only modestly, if at all, impaired and this is likely to especially affect agents dependent on liver blood flow. Other factors that affect drug elimination in the aged are drug-drug interaction and the frailty and functional impairment of many elderly, as a result of poor diet, infection, multiple hospitalizations, or other events. Decreased host defense systems in the aged liver may lead to decreased adaptation to stress and slower regeneration after injury.