Topiramate pharmacokinetics in infants

Purpose: This study's goal was to provide preliminary data on the pharmacok inetics of topiramate (TPM) in a cohort of infants (younger than 4 years) p articipating in an open-label trial of TPM in refractory infantile spasms. Methods: The pharmacokinetics of TPM were assessed in infants receiving a s table TPM dose for >7 days during the extension phase of this trial. Blood samples were drawn just before and 0.5, 1, 1.5, 2, 4, 6, 8, and 12 h after the morning TPM dose. TPM plasma concentrations were determined by fluoresc ence polarization immunoassay. The noncompartmental analysis module of WinN onlin was used to calculate individual patient pharmacokinetics profiles. Results: Five infants (ages, 23.5-29.5 months) formed the study cohort. The se infants had been given TPM for a median of 9 months (range, 6-11 months) and were currently receiving between 11 and 38.5 mg/kg/day TPM. One was re ceiving TPM monotherapy, whereas four were taking concomitant antiepileptic medications (AEDs; n = 2, enzyme-inducing agents; n = 2, non-enzyme-induci ng drugs). TPM pharmacokinetics in infants appears to be linear. In this co hort, mean TPM plasma clearance (CL/F, 66.6 +/- 27.4 ml/h/kg) was slightly higher than that reported for children and adolescents and therefore substa ntially higher than that reported for adults. TPM CL/F was higher and the c alculated half-life shorter in the infants receiving concomitant enzyme-ind ucing AEDs. Conclusions. Based on this small cohort of patients, it appears that infant s may require significantly larger TPM doses, based on weight, than childre n, adolescents, or adults. Titration to effect and not absolute TPM dose sh ould guide therapy in this age group.