Pharmacokinetic variability of new antiepileptic drugs at different ages

Newer generation antiepileptic drugs (AEDs) are increasingly used to treat epilepsies in infants, children, and the elderly. For rational prescribing in these populations, it is essential to understand the pharmacokinetic changes that occur during development and aging. Data obtained in recent years indicate that the apparent oral clearance (CL/F) of lamotrigine, topiramate, levetiracetam, oxcarbazepine, gabapentin, tiagabine, zonisamide, vigabatrin, and felbamate is considerably higher in children than in adults, the magnitude of the difference being on average in the order of 20% to 120%, depending on the drug and the age distribution of the assessed population. Information on the pharmacokinetics of these drugs in newborns is completely lacking or very sparse. Studies in the elderly have demonstrated that significant pharmacokinetic changes also occur at the other extreme of age. On average, CL/F values of newer generation AEDs have been found to be reduced by 10% to 50% compared with those found in young or middle-aged adults. These pharmacokinetic changes are clinically important and contribute to age-related differences in dosage requirements.