Waugh John, Goa Karen L
Adis International Limited, Auckland, New Zealand.
CNS Drugs. 2003;17(13):985-92. doi: 10.2165/00023210-200317130-00007.
Topiramate is an antiepileptic drug that has a broad spectrum of antiseizure effects, which appear to be the result of several neurostabilising pharmacological mechanisms. These include blockade of ion channels, potentiation of GABA neuroinhibition and glutamate receptor antagonism at non-NMDA receptors, as well as mild inhibition of carbonic anhydrase. Topiramate monotherapy dose dependently reduced the number of patients who met seizure related exit criteria in children (aged > or =6 years) and adults with epilepsy. This effect was also observed in patients who had previously experienced partial onset seizures and for those who had experienced generalised tonic clonic seizures. Six-month and 1-year seizure-free rates were dose-dependently reduced. In epilepsy, topiramate monotherapy 100 or 200 mg/day was as effective as carbamazepine 600 mg/day or valproate 1250 mg/day as measured by time to study exit for any reason, time to first seizure and percentage of patients seizure-free in the final 6 months of treatment (mean treatment duration 244 days). Adverse events associated with topiramate monotherapy that were dosage related included paraesthesia, weight loss and diarrhoea. Renal calculi were also reported in both fully published trials.
托吡酯是一种具有广泛抗癫痫作用的抗癫痫药物,其抗癫痫作用似乎是多种神经稳定药理学机制的结果。这些机制包括离子通道阻滞、GABA神经抑制增强和非NMDA受体处的谷氨酸受体拮抗作用,以及轻度碳酸酐酶抑制作用。托吡酯单药治疗剂量依赖性地减少了符合癫痫相关退出标准的儿童(年龄≥6岁)和成人患者的数量。在既往有部分性发作的患者以及有全身强直阵挛发作的患者中也观察到了这种效果。无癫痫发作6个月和1年的发生率呈剂量依赖性降低。在癫痫治疗中,以因任何原因退出研究的时间、首次发作的时间以及治疗最后6个月无癫痫发作患者的百分比(平均治疗持续时间244天)衡量,托吡酯单药治疗100或200mg/天与卡马西平600mg/天或丙戊酸1250mg/天效果相当。与托吡酯单药治疗相关的、与剂量有关的不良事件包括感觉异常、体重减轻和腹泻。在两项完整发表的试验中均报告了肾结石。