This study was performed to identify an efficacious dosing regimen for U.S. Food and Drug Administration approval of topiramate for initial monotherapy in pediatric patients aged 2-9 years diagnosed with partial onset seizures and primary generalized tonic-clonic seizures using a pharmacometric bridging approach. The approval of topiramate in monotherapy of epilepsy for adult and pediatric patients (10-15 years) was based on efficacy and safety data from clinical trials. Our analysis showed that exposure-response relationship was similar between adult and pediatric patients (6-15 years) treated with topiramate as monotherapy for epilepsy. Specific dosing in pediatric patients 2-9 years of age was derived and included in the simulations by matching predicted exposures in pediatric patients (2-9 years) to a range of exposures observed in adult and pediatric patients (6-9 years) in a previously conducted clinical trial. The analysis allowed for U.S. Food and Drug Administration approval of topiramate for initial monotherapy in pediatric patients (2-9 years).
Keywords: dosing; exposure-response; pediatric; pharmacometrics; topiramate.
Published by Elsevier Inc.