拉考沙胺与奥卡西平治疗儿童局灶性癫痫的研究进展

Research advances in lacosamide and oxcarbazepine in the treatment of focal epilepsy in children

癫痫(Epilepsy,EP)是儿童和青少年时期最常见慢性神经系统疾病之一,患病率为0.76%,约有3/4的癫痫患者于儿童时期起病。目前,关于治疗癫痫发作的手段有多种,比如口服抗癫痫发作药物(Anti-seizure medications,ASMs)、手术治疗、生酮饮食等。然而,ASMs是大部分癫痫患者首选的治疗方式,也是最重要、最基本的治疗。奥卡西平(Oxcarbazepine,OXC)与拉考沙胺(Lacosamide,LCM)都属于钠通道阻滞剂,其前者是第二代的ASMs,是一种快钠通道阻滞剂,而后者是作为第三代的ASMs,是一种慢钠通道阻滞剂。钠通道的快失活是以毫秒为单位,由内孔球链机制介导,有助于动作电位的终止和不应期的调节,是正常生理状态下主要的失活方式。与钠通道快失活不同的是,慢失活是以秒/分钟为单位,可能涉及内孔结构的重排,增加动作电位阈值调节膜的兴奋性,通常在病理状态下,钠离子通道更易进入慢失活状态。目前,OXC和LCM已被美国食品药品管理局、欧盟药品管理局和中国国家药品监督管理局批准用于4岁及以上癫痫患者局灶性起源(伴有或不伴有继发性全面发作)的单药或添加治疗。本文将对LCM和OXC在治疗儿童癫痫的药代动力学、有效性及安全性等方面的研究做出了重点介绍。

Epilepsy(EP)is one of the most common chronic nervous system disease in childhood and adolescence,with a prevalence rate of 7.6‰.About 3/4 of epilepsy patients begin to get sick in childhood.At present,there are many ways to treat epilepsy,such as oral anti-seizure medications(ASMs),surgical treatment,ketogenic diet,etc.However,ASMs are the preferred treatment for most epilepsy patients and the most important and basic treatment.Oxcarbazepine(OXC)and Lacosamide(LCM)are both sodium channel blockers.The former is a second-generation ASMs,a fast sodium channel blocker,while the latter is a third-generation ASMs,a slow sodium channel blocker.The rapid inactivation of sodium channel is mediated by the inner pore ball chain mechanism in milliseconds,which is helpful to the termination of action potential and the regulation of refractory period.It is the main inactivation mode under normal physiological conditions.Different from the rapid inactivation of sodium channels,the slow inactivation is in seconds per minute,which may involve the rearrangement of the inner pore structure and increase the excitability of the action potential threshold regulating membrane.Generally,under pathological conditions,sodium channels are more likely to enter the slow inactivation state.Now,OXC and LCM have been approved by the US Food and Drug Administration,the European Union Drug Administration,and the National Drug Administration of China for monotherapy or additive therapy of focal origin(with or without secondary generalized seizures)in epilepsy patients aged 4 years and above.This article will focus on the pharmacokinetics,efficacy,and safety of LCM and OXC in the treatment of childhood epilepsy.