Tecoma E S
UCSD Epilepsy Center, University of California, San Diego 92037, USA.
Epilepsia. 1999;40 Suppl 5:S37-46. doi: 10.1111/j.1528-1157.1999.tb00918.x.
The success of carbamazepine (CBZ) as a broad-spectrum antiepileptic drug (AED) has led to its use as first-line therapy in children and adults for partial and generalized tonic-clonic seizures. The limitations of CBZ include toxicity in sensitive individuals, autoinduction, which requires dose adjustment when therapy is initiated, and chronic hepatic induction, producing drug interactions when CBZ is used with AEDs and other drugs that undergo hepatic metabolism. One of two main products of CBZ microsomal metabolism, CBZ-10,11-epoxide (formed by oxidation of the double bond between C-10 and C-11), appears to provide antiepileptic efficacy but contributes significantly to clinical toxicity. The most common adverse effects of CBZ are central nervous system (CNS) symptoms, followed by gastrointestinal, hepatic, endocrine disturbances, and teratogenic effects. Oxcarbazepine (OXC) was developed to provide a compound chemically similar enough to CBZ to mimic its efficacy and overall safety while improving its side-effect profile. Biotransformation of OXC does not involve formation of an epoxide metabolite. Compared with the parent compound, hepatic microsomal enzyme induction and autoinduction are greatly reduced. The clinical efficacy of OXC compares favorably with CBZ in clinical trials. Clinical development of OXC began in Europe. Results of Phase I trials started to appear in the early 1980s. Controlled clinical trials, reported in the mid- to late 1980s, led to approval of OXC in many European countries, and now in over 50 nations around the world. United States multicenter clinical trials have recently been completed, and at this writing the drug is awaiting approval by the FDA. This article reviews the pharmacology, animal data, outcomes of published controlled clinical trials, postmarketing data, adverse experiences, and current recommendations for clinical use of OXC.
卡马西平（CBZ）作为一种广谱抗癫痫药物（AED）取得的成功，使其成为儿童和成人部分性及全身性强直阵挛性发作的一线治疗药物。CBZ的局限性包括对敏感个体的毒性、自身诱导作用（开始治疗时需要调整剂量）以及慢性肝酶诱导作用，当CBZ与AED及其他经肝代谢的药物合用时会产生药物相互作用。CBZ微粒体代谢的两种主要产物之一，CBZ - 10,11 - 环氧化物（由C - 10和C - 11之间的双键氧化形成）似乎具有抗癫痫疗效，但对临床毒性有显著影响。CBZ最常见的不良反应是中枢神经系统（CNS）症状，其次是胃肠道、肝脏、内分泌紊乱以及致畸作用。奥卡西平（OXC）的研发目的是提供一种化学结构与CBZ足够相似的化合物，以模拟其疗效和总体安全性，同时改善其副作用。OXC的生物转化不涉及环氧化物代谢物的形成。与母体化合物相比，肝微粒体酶诱导和自身诱导作用大大降低。在临床试验中，OXC的临床疗效与CBZ相当。OXC的临床研发始于欧洲。20世纪80年代初开始出现I期试验结果。20世纪80年代中后期报道的对照临床试验，使得OXC在许多欧洲国家获批，现在全球已有50多个国家批准使用。美国的多中心临床试验最近已经完成，撰写本文时该药物正在等待美国食品药品监督管理局（FDA）的批准。本文综述了OXC的药理学、动物实验数据、已发表的对照临床试验结果、上市后数据、不良反应以及目前的临床使用建议。
