Jain K K
Jain PharmaBiotech, Bläsiring 7, CH-4057 Basel, Switzerland.
Expert Opin Investig Drugs. 2000 Jul;9(7):1611-24. doi: 10.1517/13543784.9.7.1611.
A brief review of epilepsy as a disease, anti-epileptic drugs (AEDs) and methods of evaluation of AEDs are presented as a background for the assessment of levetiracetam which has been approved by the FDA as add-on therapy for the treatment of partial seizures with or without secondary generalisation in adults. The exact mechanism of action of levetiracetam is not known but its action differs from that of other anti-epileptic drugs. A specific binding site for levetiracetam has been identified and is possibly related to anticonvulsant activity. Levetiracetam offers an effective and broad spectrum treatment of epileptic seizures, partial as well as generalised epilepsy. Levetiracetam has been shown to be effective in genetic and kindled animal models of epilepsy and against chemoconvulsant-induced partial epileptic seizures. Levetiracetam has a near perfect pharmacokinetic profile, with rapid absorption following oral administration, excellent bioavailability, quick attainment of steady-state concentrations, linear kinetics and minimal plasma protein binding. Levetiracetam does not interact with commonly used drugs and other AEDs. In recent Phase III clinical trials, the responder rate was 39.4 - 42.1% on 3000 mg dose, compared with placebo rates of 10.9 - 16.7%. Levetiracetam has a favourable safety profile and the most frequently reported adverse events were somnolence, asthenia and dizziness. Overall, levetiracetam is considered to have several advantages over current AEDs.
本文简要回顾了癫痫这一疾病、抗癫痫药物（AEDs）以及AEDs的评估方法，以此作为评估左乙拉西坦的背景。左乙拉西坦已获美国食品药品监督管理局（FDA）批准，作为成人部分性发作伴或不伴继发性全面发作的附加治疗药物。左乙拉西坦的确切作用机制尚不清楚，但其作用与其他抗癫痫药物不同。已确定左乙拉西坦的一个特异性结合位点，其可能与抗惊厥活性有关。左乙拉西坦为癫痫发作，包括部分性癫痫和全身性癫痫，提供了一种有效且广谱的治疗方法。在癫痫的遗传和点燃动物模型以及对抗化学惊厥剂诱导的部分性癫痫发作方面，左乙拉西坦已被证明是有效的。左乙拉西坦具有近乎完美的药代动力学特征，口服给药后吸收迅速，生物利用度极佳，能快速达到稳态浓度，呈线性动力学且血浆蛋白结合率极低。左乙拉西坦不与常用药物及其他抗癫痫药物相互作用。在近期的III期临床试验中，3000mg剂量组的有效率为39.4 - 42.%,而安慰剂组的有效率为10.9 - 16.7%。左乙拉西坦具有良好的安全性，最常报告的不良事件为嗜睡、乏力和头晕。总体而言，与目前的抗癫痫药物相比，左乙拉西坦被认为具有多个优势。
