Almeida Luis, Minciu Ioana, Nunes Teresa, Butoianu Nicolina, Falcão Amilcar, Magureanu Sandra-Adriana, Soares-da-Silva Patrício
Department of Research and Development, BIAL, A Av. da Siderurgia Nacional, 4745-457 S. Mamede do Coronado, Portugal.
J Clin Pharmacol. 2008 Aug;48(8):966-77. doi: 10.1177/0091270008319706. Epub 2008 May 28.
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.
本研究调查了新型电压门控钠通道阻滞剂醋酸艾司利卡西平（ESL）在2至7岁癫痫儿童（n = 11）、7至11岁癫痫儿童（n = 8）以及12至17岁青少年癫痫患者（n = 10）中的药代动力学。该研究还探讨了ESL的疗效和耐受性。患者在第1至4周接受ESL每日5 mg/kg的剂量治疗，第5至8周接受15 mg/kg/天的剂量治疗，第9至12周接受30 mg/kg/天（或1800 mg/天，以较低者为准）的剂量治疗。在每个4周治疗期结束时，进行24小时药代动力学分析。与成人相似，ESL迅速代谢为艾司利卡西平。在所有年龄组中，ESL给药后0.5至3小时达到艾司利卡西平的峰值浓度，C(max)和AUC(0 - 24)与剂量呈比例关系。给予相同ESL剂量/kg后，各年龄组间艾司利卡西平的C(max)相似，但由于年幼儿童相比青少年艾司利卡西平的血浆清除更快，AUC(0 - 24)取决于年龄。R - 利卡西平和奥卡西平是次要代谢产物。在2至7岁儿童和12至17岁青少年中观察到癫痫发作频率呈剂量依赖性降低，但在7至11岁儿童中未观察到。每组各有1例患者癫痫发作停止。ESL总体耐受性良好。
