Doty Pamela, Rudd G David, Stoehr Thomas, Thomas Dirk
SCHWARZ BIOSCIENCES, Inc., Research Triangle Park, North Carolina 27709, USA.
Neurotherapeutics. 2007 Jan;4(1):145-8. doi: 10.1016/j.nurt.2006.10.002.
Lacosamide is a new chemical entity being investigated as an adjunctive treatment for epilepsy, as well as monotherapy for diabetic neuropathic pain. Lacosamide appears to have a dual mode of action: selective enhancement of sodium channel inactivation and modulation of collapsin response mediator protein-2. Rapidly and completely absorbed after oral administration, lacosamide has an elimination half-life of approximately 13 hours and a low potential for drug interactions. Additionally, lacosamide exhibits linear, dose-proportional pharmacokinetics with low intra- and interpatient variability. Randomized controlled trials of adjunctive lacosamide (200, 400, and 600 mg/day) have demonstrated statistically significant reduction in median seizure frequency compared with placebo. In addition, 50% responder rates for lacosamide (400 and 600 mg/day) were statistically superior to placebo. The most frequently reported adverse events (> or =10% of lacosamide-treated patients) included dizziness, headache, and nausea. A double-blind, double-dummy randomized trial of intravenous lacosamide (30- and 60-minute infusion) as replacement for oral lacosamide showed that the safety and tolerability profiles were comparable for intravenous and oral lacosamide. The efficacy and safety results from completed clinical trials, as well as the favorable pharmacokinetic profile, suggest that lacosamide may represent a significant advance in antiepileptic drug therapy.
拉科酰胺是一种正在研究用于癫痫辅助治疗以及糖尿病性神经病理性疼痛单一疗法的新型化学实体。拉科酰胺似乎具有双重作用模式：选择性增强钠通道失活和调节塌陷反应介导蛋白-2。口服给药后迅速且完全吸收，拉科酰胺的消除半衰期约为13小时，药物相互作用的可能性较低。此外，拉科酰胺呈现线性、剂量成正比的药代动力学，患者内和患者间变异性低。拉科酰胺（200、400和600毫克/天）辅助治疗的随机对照试验表明，与安慰剂相比，癫痫发作中位数频率有统计学意义的显著降低。此外，拉科酰胺（400和600毫克/天）的50%缓解率在统计学上优于安慰剂。最常报告的不良事件（≥接受拉科酰胺治疗患者的10%）包括头晕、头痛和恶心。一项将静脉注射拉科酰胺（30分钟和60分钟输注）作为口服拉科酰胺替代疗法的双盲、双模拟随机试验表明，静脉注射和口服拉科酰胺的安全性和耐受性相当。已完成临床试验的疗效和安全性结果，以及良好的药代动力学特征，表明拉科酰胺可能代表抗癫痫药物治疗的一项重大进展。
