Cawello Willi, Stockis Armel, Andreas Jens-Otto, Dimova Svetlana
UCB Pharma, Monheim, Germany.
Ann N Y Acad Sci. 2014 Nov;1329:18-32. doi: 10.1111/nyas.12513. Epub 2014 Aug 28.
Lacosamide (LCM) is a functionalized amino acid specifically developed for use as an antiepileptic drug (AED) and is currently indicated as adjunctive treatment for partial-onset seizures in adults with focal epilepsy (maximum approved dose 400 mg/day). Characterization of the pharmacokinetic profile is an important aspect in the development of LCM. Studies in healthy subjects and in patients with focal epilepsy have established that LCM has several favorable pharmacokinetic characteristics, including rapid absorption and high oral bioavailability not affected by food, linear and dose-proportional pharmacokinetics, low inter- and intraindividual variability, low plasma protein binding, renal elimination, and a low potential for clinically relevant pharmacokinetic drug-drug interactions both with AEDs and other common medications. Studies have demonstrated bioequivalence among the three LCM formulations (oral tablets, oral solution, and solution for intravenous (IV) infusion), allowing direct conversion to or from oral and IV administration without titration. Thus, the favorable and predictable pharmacokinetic profile and bioequivalence of LCM formulations, coupled with the low potential for clinically relevant pharmacokinetic drug-drug interactions, make LCM an easy-to-use adjunctive treatment for the management of patients with focal epilepsy.
拉科酰胺（LCM）是一种专门开发用作抗癫痫药物（AED）的功能化氨基酸，目前被指定为局灶性癫痫成年患者部分性发作的辅助治疗药物（最大批准剂量为400毫克/天）。药代动力学特征的表征是拉科酰胺开发中的一个重要方面。在健康受试者和局灶性癫痫患者中进行的研究表明，拉科酰胺具有几个有利的药代动力学特征，包括吸收迅速、不受食物影响的高口服生物利用度、线性和剂量成比例的药代动力学、个体间和个体内变异性低、血浆蛋白结合率低、经肾排泄，以及与AED和其他常用药物发生临床相关药代动力学药物相互作用的可能性低。研究表明，三种拉科酰胺制剂（口服片剂、口服溶液和静脉输注溶液）具有生物等效性，无需滴定即可直接在口服和静脉给药之间转换。因此，拉科酰胺制剂良好且可预测的药代动力学特征和生物等效性，再加上临床相关药代动力学药物相互作用的可能性低，使得拉科酰胺成为管理局灶性癫痫患者的一种易于使用的辅助治疗药物。
