Adis, a Wolters Kluwer Business, Auckland, New Zealand.
Drugs. 2011 Mar 5;71(4):489-514. doi: 10.2165/11204490-000000000-00000.
Levetiracetam (Keppra®, E Keppra®) is an established second-generation antiepileptic drug (AED). Worldwide, levetiracetam is most commonly approved as adjunctive treatment of partial onset seizures with or without secondary generalization; other approved indications include monotherapy treatment of partial onset seizures with or without secondary generalization, and adjunctive treatment of myoclonic seizures associated with juvenile myoclonic epilepsy and primary generalized tonic-clonic (GTC) seizures associated with idiopathic generalized epilepsy. Levetiracetam has a novel structure and unique mechanisms of action. Unlike other AEDs, the mechanisms of action of levetiracetam appear to involve neuronal binding to synaptic vesicle protein 2A, inhibiting calcium release from intraneuronal stores, opposing the activity of negative modulators of GABA- and glycin-gated currents and inhibiting excessive synchronized activity between neurons. In addition, levetiracetam inhibits N-type calcium channels. Levetiracetam is associated with rapid and complete absorption, high oral bioavailability, minimal metabolism that consists of hydrolysis of the acetamide group, and primarily renal elimination. It lacks cytochrome P450 isoenzyme-inducing potential and is not associated with clinically significant pharmacokinetic interactions with other drugs, including other AEDs. The efficacy of oral immediate-release levetiracetam in controlling seizures has been established in numerous randomized, double-blind, controlled, multicentre trials in patients with epilepsy. Adjunctive levetiracetam reduced the frequency of seizures in paediatric and adult patients with refractory partial onset seizures to a significantly greater extent than placebo. Monotherapy with levetiracetam was noninferior to that with carbamazepine controlled release in controlling seizures in patients with newly diagnosed partial onset seizures. Levetiracetam also provided seizure control relative to placebo as adjunctive therapy in patients with idiopathic generalized epilepsy with myoclonic seizures or GTC seizures. In addition, patients receiving oral levetiracetam showed improvements in measures of health-related quality of life relative to those receiving placebo. Although treatment-emergent adverse events were commonly reported in the clinical trials of levetiracetam, the overall proportion of patients who experienced at least one treatment-emergent adverse event was broadly similar in the levetiracetam and placebo treatment groups, with most events being mild to moderate in severity. Levetiracetam is not associated with cognitive impairment or drug-induced weight gain, but has been associated with behavioural adverse effects in some patients.
左乙拉西坦（开浦兰®，E 开浦兰®）是一种已被广泛应用的第二代抗癫痫药物（AED）。在全球范围内，左乙拉西坦最常用于辅助治疗部分发作性癫痫，伴或不伴继发性全面发作；其他批准的适应症包括部分发作性癫痫的单药治疗，伴或不伴继发性全面发作，以及辅助治疗与青少年肌阵挛性癫痫相关的肌阵挛性癫痫和与特发性全面性癫痫相关的原发性全面强直-阵挛（GTC）发作。左乙拉西坦具有独特的结构和作用机制。与其他 AED 不同，左乙拉西坦的作用机制似乎涉及神经元与突触囊泡蛋白 2A 的结合，抑制细胞内钙库从神经元内释放，拮抗 GABA 和甘氨酸门控电流的负调节剂的活性，并抑制神经元之间过度同步的活动。此外，左乙拉西坦抑制 N 型钙通道。左乙拉西坦具有快速和完全吸收、高口服生物利用度、水解乙酰酰胺基团为主的最小代谢以及主要经肾脏消除的特点。它缺乏细胞色素 P450 同工酶诱导潜力，与其他药物（包括其他 AED）之间不存在具有临床意义的药代动力学相互作用。在多项随机、双盲、对照、多中心临床试验中，口服速释左乙拉西坦控制癫痫发作的疗效已得到证实。与安慰剂相比，添加左乙拉西坦可显著减少儿童和成年难治性部分发作性癫痫患者的癫痫发作频率。左乙拉西坦单药治疗与卡马西平控释片治疗新诊断的部分发作性癫痫的疗效相当。左乙拉西坦作为辅助治疗在特发性全面性癫痫伴肌阵挛性癫痫或 GTC 发作患者中也能控制癫痫发作。此外，与安慰剂相比，接受口服左乙拉西坦治疗的患者在健康相关生活质量方面有所改善。尽管在左乙拉西坦的临床试验中经常报告治疗出现的不良事件，但左乙拉西坦治疗组和安慰剂治疗组中至少出现一次治疗出现的不良事件的患者比例大致相似，大多数事件的严重程度为轻度至中度。左乙拉西坦与认知障碍或药物引起的体重增加无关，但在一些患者中与行为不良事件有关。
