Oxcarbazepine pharmacokinetics and tolerability in children with inadequately controlled epilepsy.

Author(s): Rey E, Bulteau C, Motte J, Tran A, Sturm Y, D'Souza J, Markabi S, Pons G, Dulac O

Affiliation(s): Hopital St. Vincent de Paul, 74, Avenue Denfert-Rochereau, 75 674 Paris Cedex 14, France.

Publication date & source: 2004-11, J Clin Pharmacol., 44(11):1290-300.

Publication type: Clinical Trial; Multicenter Study; Randomized Controlled Trial

This two-part, open-label study evaluated the pharmacokinetics, safety, and tolerability of oxcarbazepine as combination therapy in 112 children 2 to 12 years old with inadequately controlled epilepsy. Part I was a pharmacokinetic study in children stratified by age (2-5 years and 6-12 years) and randomized to receive a single oxcarbazepine dose of 5 mg/kg or 15 mg/kg. Mean specific AUC and t(1/2) values of the active metabolite (MHD) were approximately 30% lower in younger children compared with older children, regardless of dose. Part II was a 4-month safety, tolerability, and pharmacokinetic study in which children received oxcarbazepine doses of 11 to 68 mg/kg/day. The mean specific oxcarbazepine daily dose was 38% higher in younger children compared with older children. Similarly, mean trough plasma MHD concentrations were 34% lower in younger children. Six (5%) children discontinued due to adverse events. Oxcarbazepine was safe and well tolerated. Younger children require higher oxcarbazepine doses because of rapid clearance.