Short communicationTopiramate pharmacokinetics in infants and young children: Contribution of population analysis

SummaryPurposeTo determine the range of topiramate (TPM) concentrations obtained in children under 4 with the recommended dosage regimen (3-9 mg/kg/day) and to compare them to adult target ranges.MethodsThe population pharmacokinetic model developed for TPM, with/without enzyme inducer antiepileptic drugs (EIAEDs) in children was used to determine dosage regimens providing AUC and trough concentrations (Ctroughs) within the adult ranges.ResultsTPM pharmacokinetics was described by a one-compartment model. EIAEDs increased the apparent clearance (CL/F) and age and body weight increased the apparent distribution volume (Vd/F). Mean population estimates (% CV interindividual variability) were 0.608/1.15 L/h (13%) for CL/F without/with EIAEDs, 28.6 L (0.2%) for Vd/F and 1.4 h−1 (124%) for the absorption rate constant. Mean AUC0-12 h reached with a 2 mg/kg/day dosing regimen was within described range. A 6-16 mg/kg/day dose depending on age allowed reaching target Ctrough range with the highest probability. Combined EIAEDs led to a 2- and 3-fold decrease in AUC and Ctrough, respectively.ConclusionTPM dosage of 2/4 mg/kg/day (without/with EIEADs, respectively) provides the AUC reported in adults. In children under 4, alternative dosing regimen should be considered mainly when associated to EIAED to reach Ctrough comparable to adult values.