Abstract: Stiripentol (marketed by Biocodex as Diacomit?) is an anticonvulsant drug, structurally unrelated to any other compound, which has recently been approved as adjunctive therapy with clobazam and valproate for Dravet syndrome in Europe, Canada, and Japan. This rare form of early childhood epilepsy is associated with subsequent cognitive impairment, significant risk of death, and high pharmacoresistance. Based on an efficacy signal of stiripentol added to clobazam and valproate in an observational, prospectively conducted, exploratory study including 10% of children with Dravet syndrome, a randomized placebo-controlled trial was specifically dedicated to patients with Dravet syndrome inadequately controlled by clobazam and valproate. Results showed significantly higher responder rates (71% versus 5%; P<0.0001) and decrease in seizure frequency (-69% versus +7%; P<0.002) on stiripentol than on placebo. A second, independently performed, randomized controlled trial confirmed these results 2 years later, and both trials were plotted in a meta-analysis. Efficacy was supported by three subsequent observational studies, with, respectively, 46 (France), 23 (Japan), and 82 (USA) children with Dravet syndrome treated with stiripentol for up to 5 years. Based on the experiences of more than 2,000 patients with Dravet syndrome who were exposed to stiripentol, drowsiness, loss of appetite, and weight loss are the most frequent adverse events and may be reduced by decreasing the dosage of co-medication. The inhibition of stiripentol by the cytochrome P450 complex (CYP2C19, and CYP3A4) leads to clinically significant interactions. Experimental data, both in vitro and in vivo, have definitively established that stiripentol is a GABAergic anticonvulsant and acts on different sites than benzodiazepines. The pharmacodynamic interactions also enhance the anticonvulsant effect of the stiripentol–clobazam combination in patients with Dravet syndrome, irrespective of the GABAergic effect. Stiripentol is currently the only drug specifically indicated in Dravet syndrome.
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机译：摘要：Stiripentol（由Biocodex以Diacomit？出售）是一种抗惊厥药，在结构上与任何其他化合物均无关联，最近已在欧洲，加拿大和日本被批准与氯巴沙姆和丙戊酸盐作为Dravet综合征的辅助疗法。儿童癫痫病的这种罕见形式与随后的认知障碍，重大死亡风险和高药物耐受性有关。根据一项在一项观察性，前瞻性，探索性研究中（包括10％患有Dravet综合征的儿童）的一项观察性，探索性研究中，加入了stripentol的疗效信号，一项随机安慰剂对照试验专门针对了clobazam和valproate控制不足的Dravet综合征患者。结果显示，替比替多对安慰剂的应答率明显更高（71％对5％; P <0.0001），癫痫发作频率降低（-69％对+ 7％; P <0.002）。另一项独立进行的随机对照试验于2年后证实了这些结果，并将两项试验均纳入荟萃分析。后来的三项观察性研究支持了有效性，分别对46名（法国），23名（日本）和82名（美国）患有Dravet综合征的儿童进行了瑞替普坦治疗，长达5年。根据2,000多名Dravet综合征患者的经验，他们暴露于替比妥特后，嗜睡，食欲不振和体重减轻是最常见的不良事件，可以通过减少联合用药的剂量来减轻。细胞色素P450复合物（CYP2C19和CYP3A4）对甲氧苯萘酚的抑制作用导致临床上显着的相互作用。体外和体内的实验数据已确定地确定，替比妥特是一种GABA能抗惊厥药，其作用部位与苯并二氮杂s不同。不管GABA的药效是什么，药效学相互作用还增强了替瑞芬特-克洛巴沙姆组合对Dravet综合征患者的抗惊厥作用。 Stiripentol是目前在Dravet综合征中特别指出的唯一药物。
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