Pharmacokinetics, efficacy, and tolerability of eslicarbazepine acetate in children and adolescents with epilepsy.
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.
Department of Research and Development, BIAL, A Av. da Siderurgia Nacional, 4745-457 S. Mamede do Coronado, Portugal.
Luis
L
Almeida
Ioana
I
Minciu
Teresa
T
Nunes
Nicolina
N
Butoianu
Amilcar
A
Falcão
Sandra-Adriana
SA
Magureanu
Patrício
P
Soares-da-Silva
D000293:Adolescent; D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D003984:Dibenzazepines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004351:Drug Resistance; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D012640:Seizures / Q000139:chemically induced
D000927:Anticonvulsants; D003984:Dibenzazepines; C416835:eslicarbazepine acetate