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 which the approach to therapy in elderly patients can be based on pharmacokinetic data. Both healthy aging and comorbid disease can alter the responsiveness of the body to drugs and to their absorption, distribution and elimination. Altered absorption in the elderly has not been documented after oral ingestion of any anticonvulsant drug. Increased adipose tissue in the elderly may raise the apparent volume of distribution (Vd) of lipid-soluble drugs. An increased Vd in the elderly has been shown for diazepam and clobazam, but not midazolam. The data are inconclusive for phenytoin and valproic acid (sodium valproate). The decreased plasma protein binding that often occurs in the elderly has few clinical consequences. The reduced liver function that to occur with aging seems to affect the elimination of drugs that are mainly cleared by oxidative metabolism [e.g. carbamazepine, phenytoin and phenobarbital (phenobarbitone)]. Reduced clearances for methylphenobarbital (methylphenobarbitone), diazepam, midazolam and clobazam occur in elderly men, but not in women. The reduced renal function that is seen in old age affects the disposition of drugs that are eliminated mainly by direct renal excretion. Thus. the clearances of vigabatrin and gabapentin correlate with creatinine clearance. Such considerations may help guide anticonvulsant dosage in the elderly.