The potential for vigabatrin-induced intramyelinic edema in humans
The potential for vigabatrin-induced intramyelinic edema in humans
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DOI：
10.1111/j.1528-1157.2000.tb00134.x
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发表时间：
2000-02-01
期刊：
影响因子：
5.6
通讯作者：
Sze, G
中科院分区：
文献类型：
--
作者：
Cohen, JA;Fisher, RS;Sze, G
目的：Vigabatrin （Sabril, Hoechst Marion Roussel）是一种抗癫痫药物（AED），目前在64个国家上市，用于治疗部分和继发性全发性癫痫发作。Vigabatrin （VGB）在这些国家的一部分市场上销售，用于治疗婴儿痉挛。人体临床经验表明，VGB可有效控制癫痫发作，且安全范围广。然而，动物毒性研究引起了人们的关注，因为在一些实验动物物种中，长期给药VGB被证明会诱导髓内水肿（IME）。方法：回顾了关于vgb诱导IME的可能性的动物和人类数据。对在临床试验中或通过处方接受VGB的患者的监测已经进行了大约15年，以确定出现可能与IME相关的临床异常的患者。结果：VGB诱发动物IME的组织学病变可可靠再现，并与多模态诱发电位（EPs）和磁共振成像（MRI）的变化相关，大量关于VGB对癫痫患者EP和MRI影响的研究表明，在这些模式中没有明确的IME相关变化。此外，对vgb治疗患者的尸检和手术脑样本进行了潜在的IME组织病理学检查。在估计的35万患者年的VGB暴露中（类似于17.5万患者在平均剂量为2g /天的情况下暴露2年），没有确定的VGB诱发IME病例。结论：对各种来源数据的综合审查未能确定任何使用VGB治疗的人类IME病例。
Purpose: Vigabatrin (Sabril, Hoechst Marion Roussel) is an antiepilepsy drug (AED) presently marketed in 64 countries for the treatment of partial and secondarily generalized seizures. Vigabatrin (VGB) is marketed in a subset of these countries for the treatment of infantile spasms. Clinical experience in humans has shown that VGB provides effective seizure control with a wide margin of safety. However, animal toxicity studies raised concern when prolonged administration of VGB was shown to induce intramyelinic edema (IME) in some laboratory animal species.Methods: Animal and human data were reviewed with respect to the potential for VGB-induced IME. Surveillance of patients receiving VGB in clinical trials or by prescription has been conducted for >15 years to identify patients developing clinical abnormalities that might be IME related.Results: The histologic lesions of VGB-induced IME in animals are reliably reproduced and correlate with changes in multimodality evoked potentials (EPs) and magnetic resonance imaging (MRI), Numerous studies of the effects of VGB on EP and MRI in epilepsy patients have demonstrated no clear-cut IME-related changes in these modalities. Additionally, autopsy and surgical brain samples from VGB-treated patients have been scrutinized for potential IME histopathology. In an estimated 350,000 patient-years of VGB exposure (similar to 175,000 patients exposed for 2 years at an average dose of 2 g/day), no definite case of VGB-induced IME has been identified.Conclusions: Comprehensive review of a variety of sources of data failed to identify any definite case of IME in humans treated with VGB.