Metabolism of antiepileptic medication: newborn to elderly.

Abstract

Epilepsy affects individuals of all ages. Regimens of antiepileptic drugs (AEDs) and side-effect profiles differ for infants, children, adults, and the elderly. Thus, the epileptologist must be familiar with the specific changes of AED metabolism with age. In general, metabolic rates are fastest in children; therefore, AED half-lives are shortest in this group. Rates of AED elimination are slowest in neonates, infants, and children. Thus, children need larger dosages, on a mg/kg basis, than adults. The usual phenytoin (PHT) dosage in adults is 4-6 mg/kg per day, but children may need a dosage three to five times higher. On the other hand, the PHT dosages in the elderly may need to be 3-4 mg/kg per day to achieve therapeutic levels. Likewise, the half-life of carbamazepine (CBZ) is shortest in children and the elderly. Profiles of metabolites may also be age-specific, a difference of particular importance for valproate (VPA). The relative amount of VPA metabolized to 4-ene is more than twofold less in adults than in children, which may explain the different profile of hepatotoxicity seen by age. The elderly may be more vulnerable to adverse effects of AEDs. Many elderly have neurologic deficits that may render them more vulnerable to neurotoxic effects such as ataxia and cognitive disturbances. Also, low serum albumin concentrations, which result in decreased binding, may mask high serum AED concentrations. The hyponatremia associated with CBZ may be a particular concern in the elderly. Gingival hyperplasia, a concern in children, may not be a problem in the elderly.