ANTICONVULSANT THERAPY IN AGED PATIENTS - CLINICAL PHARMACOKINETIC CONSIDERATIONS

Alterations in drug disposition that occur with aging are now becoming widely recognised, and there is an increasing number of drugs for whi ch the approach to therapy in elderly patients can be based on pharmac okinetic data. both healthy aging and comorbid disease can alter the r esponsiveness of the body to drugs and to their absorption, distributi on and elimination. Altered absorption in the elderly has not been doc umented after oral ingestion of any anticonvulsant drugs. Increased ad ipose tissue in the elderly may raise the apparent volume of distribut ion (Vd) of lipid-soluble drugs. An increased Vd in the elderly has be en shown for diazepam and clobazam, but not midazolam. The data are in conclusive for phenytoin and valproic acid (sodium valproate). The dec reased plasma protein binding that often occurs in the elderly has few clinical consequences. The reduced liver function that tends to occur with aging seems to affect the elimination of drugs that are mainly c leared by oxidative metabolism [e.g. carbamazepine, phenytoin and phen obarbital (phenobarbitone)]. Reduced clearances for methylphenobarbita l (methylphenobarbitone), diazepam, midazolam and clobazam occur in el derly men, but not in women. The reduced renal function that is seen i n old age affects the disposition of drugs that are eliminated mainly by direct renal excretion. Thus, the clearances of vigabatrin and gaba pentin correlate with creatinine clearance. Such considerations may he lp guide anticonvulsant dosage in the elderly.