Department of Research and Development, BIAL, S Mamede do Coronado, Portugal.
Acta Neurol Scand. 2010 Apr;121(4):257-64. doi: 10.1111/j.1600-0404.2009.01233.x. Epub 2009 Dec 28.
Anti-epileptic drugs are often used in combination. Both eslicarbazepine (main metabolite of eslicarbazepine acetate, ESL) and lamotrigine undergo conjugation with glucuronic acid, and both eslicarbazepine and its glucuronide and lamotrigine glucuronide undergo extensive renal elimination; therefore, there is a potential for interaction. This study investigated the interaction between ESL and lamotrigine in healthy subjects.
Open-label study in two parallel groups of 16 healthy volunteers each. After an 8-day treatment with ESL or lamotrigine, ESL (1200 mg once-daily) and lamotrigine (150 mg once-daily) were co-administered for 19 days. Geometric mean ratios (GMR) and 90% confidence intervals (90% CI) for maximum plasma concentration (C(max)) and area under the plasma concentration-time curve in the dosing interval (AUC(0-24)) were calculated for eslicarbazepine (ESL active metabolite) and lamotrigine.
The C(max) and AUC(0-24) GMR (90% CI) were, respectively, 95% (87-102%) and 96% (91-102%) for eslicarbazepine, and 88% (82-94%) and 86% (81-92%) for lamotrigine. The 90% CI of the C(max) and AUC(0-24) GMR fell within the prespecified acceptance interval (80-125%) both for eslicarbazepine and lamotrigine.
There was no significant pharmacokinetic interaction between ESL and lamotrigine in healthy subjects. Therefore, no dosage adjustment appears to be usually required in either lamotrigine or ESL when the drugs are co-administered.
抗癫痫药物通常联合使用。艾司利卡西平（艾司利卡西平醋酸盐的主要代谢物，ESL）和拉莫三嗪均与葡萄糖醛酸结合，ESL 及其葡萄糖醛酸化物和拉莫三嗪葡萄糖醛酸化物均广泛经肾脏消除；因此，存在相互作用的潜力。本研究旨在调查健康受试者中 ESL 与拉莫三嗪之间的相互作用。
这是一项开放标签、两平行组研究，每组 16 名健康志愿者。ESL 或拉莫三嗪治疗 8 天后，19 天内共给予 ESL（每日一次 1200mg）和拉莫三嗪（每日一次 150mg）。计算艾司利卡西平和拉莫三嗪的最大血浆浓度（C(max)）和给药间隔内的血浆浓度-时间曲线下面积（AUC(0-24)）的几何均数比值（GMR）及其 90%置信区间（90%CI）。
艾司利卡西平的 C(max)和 AUC(0-24)GMR（90%CI）分别为 95%（87-102%）和 96%（91-102%），拉莫三嗪分别为 88%（82-94%）和 86%（81-92%）。艾司利卡西平和拉莫三嗪的 C(max)和 AUC(0-24)GMR 的 90%CI 均落在预设的可接受区间（80-125%）内。
在健康受试者中，ESL 与拉莫三嗪之间无显著的药代动力学相互作用。因此，当两种药物同时使用时，拉莫三嗪或 ESL 通常不需要调整剂量。
