Evaluation of pharmacokinetics, safety and efficacy of topiramate in children with localization-related epilepsy

We evaluated the pharmacokinetics, safety and efficacy of topiramate (TPM) 1 to 9 mg/kg/day as an adjunctive therapy to other antiepileptic drug(s) in 27 Japanese children (2 to 15 years old) with symptomatic or cryptogenic localization-related epilepsy. Trough concentrations increased almost dose-dependently within the dose range of 1 to 9 mg/kg/day after repeated oral administration of topiramate twice daily. Maximum drug concentration (C _max) and area under the plasma concentration-time curve (AUC) were approximately 1.5 times higher and approximately 1.8 times larger, respectively, in children not receiving concomitant enzyme-inducing antiepileptic drug(s) than in those concomitantly receiving such drug(s). The major adverse drug reactions were somnolence, decreased blood bicarbonate, decreased appetite, and decreased weight. The median percentage reduction in epileptic seizure rate during the pharmacokinetic study was 41.2%. Pharmacokinetics in Japanese children were almost the same as those reported for a foreign pharmacokinetic study in epileptic children. No adverse drug reactions forcing a discontinuation of treatment were observed.