DRUG DISPOSITION AND HEPATOTOXICITY IN THE ELDERLY

Overall, the aged liver seems to function remarkably well in the elder ly. Decreased drug disposition is selective and modest and there is no compelling evidence of greater susceptibility to drug-induced or othe r types of injury. Drug-drug interactions and concurrent derangements accompanying advanced age may, however, contribute to adverse drug eff ects. Still, the aged, consume about three times as many therapeutic a gents as other people. Most of these are metabolized in the liver befo re excretion. With increasing age, hepatic blood flow falls and so doe s hepatic volume. Moreover, binding of some agents normally carried on albumin may decrease. In contrast, increasing age has relatively mode st 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 th e aged are drug-drug interaction and the frailty and functional impair ment of many elderly, as a result of poor diet, infection, multiple ho spitalizations, or other events. Decreased host defense systems in the aged liver may lead to decreased adaptation to stress and slower rege neration after injury.