Pharmacokinetics, efficacy, and tolerability of eslicarbazepine acetate in children and adolescents with epilepsy

J Clin Pharmacol. 2008 Aug;48(8):966-77. doi: 10.1177/0091270008319706. Epub 2008 May 28.

Abstract

This study investigates the pharmacokinetics of eslicarbazepine acetate (ESL), a new voltage-gated sodium channel blocker, in epileptic children aged 2 to 7 years (n = 11) and 7 to 11 years (n = 8) and adolescents aged 12 to 17 years (n = 10). The study explores ESL efficacy and tolerability. Patients were treated with ESL once-daily doses of 5 mg/kg/day on weeks 1 to 4, 15 mg/kg/day on weeks 5 to 8, and 30 mg/kg/day (or 1800 mg/day, whichever was less) on weeks 9 to 12. At the end of each 4-week period, a 24-hour pharmacokinetic profiling was performed. Similar to adults, ESL was rapidly metabolized to eslicarbazepine. In all age groups, eslicarbazepine peak concentrations were reached 0.5 hour to 3 hours after ESL dosing, and C(max) and AUC(0-24) were dose proportional. Eslicarbazepine C(max) was similar between age groups following administration of identical ESL dose/kg, but AUC(0-24) depended on age due to a faster plasma clearance of eslicarbazepine in younger children compared with adolescents. R-licarbazepine and oxcarbazepine were minor metabolites. A dose-dependent decrease in seizure frequency was observed in children aged 2 to 7 years and adolescents aged 12 to 17 years but not in children aged 7 to 11 years. One patient in each group became seizure free. ESL was generally well tolerated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anticonvulsants / adverse effects
  • Anticonvulsants / pharmacokinetics*
  • Anticonvulsants / pharmacology*
  • Area Under Curve
  • Child
  • Child, Preschool
  • Dibenzazepines / adverse effects
  • Dibenzazepines / pharmacokinetics*
  • Dibenzazepines / pharmacology*
  • Drug Resistance
  • Epilepsy / drug therapy*
  • Epilepsy / metabolism*
  • Female
  • Half-Life
  • Humans
  • Male
  • Seizures / chemically induced

Substances

  • Anticonvulsants
  • Dibenzazepines
  • eslicarbazepine acetate