Jain K K
Jain PharmaBiotech, Bläsiring 7, CH-4057 Basel, Switzerland.
Expert Opin Pharmacother. 2000 Sep;1(6):1245-60. doi: 10.1517/14656566.1.6.1245.
A brief review of epilepsy as a disease, anti-epileptic drugs and methods of evaluation of anti-epileptic drugs are presented as a background for assessment of zonisamide, which has been approved by the FDA as add-on therapy for the treatment of partial seizures with or without secondary generalisation in adults. Chemically, zonisamide is classified as a sulphonamide and is unrelated to other anti-epileptic drugs. The mode of action of zonisamide remains unclear, but likely mechanisms are blockade of sodium and T-type calcium channels. It is also shown to have some neuroprotective effect against hypoxia and ischaemia. It has a liner pharmacokinetics with excellent oral bioavailability. Zonisamide has been approved for use in Japan for ten years prior to approval in USA and Europe. Clinical experience with zonisamide in Japan has documented its efficacy in the treatment of partial seizures (partial-onset generalised tonic-clonic, simple partial and/or complex partial seizures) and to a more variable extent, generalised tonic-clonic, generalised tonic (mainly seen in symptomatic generalised epilepsies including Lennox-Gastaut Syndrome) and compound/combination seizures. The efficacy and safety was confirmed in trials conducted in USA and Europe in adults as well as children. Zonisamide compares favourably with other newly introduced drugs and has the potential for development as a monotherapy for epilepsy.
作为评估唑尼沙胺的背景,本文简要回顾了癫痫这种疾病、抗癫痫药物以及抗癫痫药物的评估方法。唑尼沙胺已获美国食品药品监督管理局(FDA)批准,作为成人伴有或不伴有继发性全面发作的部分性癫痫发作的附加疗法。从化学角度来看,唑尼沙胺属于磺酰胺类,与其他抗癫痫药物无关。唑尼沙胺的作用机制尚不清楚,但可能的机制是阻断钠通道和T型钙通道。它还显示出对缺氧和缺血具有一定的神经保护作用。其具有线性药代动力学,口服生物利用度极佳。唑尼沙胺在获得美国和欧洲批准之前,已在日本获批使用十年。在日本,唑尼沙胺的临床经验已证明其在治疗部分性癫痫发作(部分性发作继发全面强直阵挛发作、单纯部分性发作和/或复杂部分性发作)方面的疗效,在一定程度上,对全面强直阵挛发作、全面强直发作(主要见于症状性全面性癫痫,包括Lennox-Gastaut综合征)以及复合/联合发作也有疗效。在美国和欧洲针对成人及儿童开展的试验中,唑尼沙胺的疗效和安全性得到了证实。唑尼沙胺与其他新推出的药物相比具有优势,有潜力发展成为癫痫的单一疗法。