Preliminary observations on topiramate in pediatric epilepsies

Preliminary results of studies of topiramate (TPM) in children are now available. In a pharmacokinetic study among 18 male and female children, target daily dosages of up to 9 mg/kg/day were evaluated. TPM pharmacokinetics in children were linear. Mean TPM oral clearance (CL/F) was 44-54% higher in children [depending on concomitant antiepileptic drugs (AEDs)] compared with historical data from adults, and steady-state plasma TPM concentrations for the same mg/kg dose were 33% lower in children compared with historical adult data. In a long-term, open-label pilot study of adjunctive TPM therapy in 18 patients with Lennox-Gastaut syndrome, six of the eight patients (75%) still receiving TPM report a greater than 50% reduction in total seizures, with the best results observed in tonic-atonic, atypical absence, and generalized tonic-clonic seizures. Subsequent large double-blind, placebo-controlled trials of adjunctive TPM therapy in Lennox-Gastaut syndrome and refractory partial-onset pediatric epilepsy are ongoing, with high percentages of enrolled patients in both studies completing double-blind treatment and entering long-term TPM open extension trials. A small TPM monotherapy substitution trial in children with well controlled partial onset seizures showed that TPM monotherapeutic substitution can be achieved successfully with an acceptable amount of adverse experiences with a weekly increase of 1 mg/kg/day to a maximal dose of 3 mg/kg/day. These preliminary results suggest that TPM may be a useful new AED in pediatric patients with a variety of seizure disorders.