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氨己烯酸的特性及其在部分发作性癫痫治疗中的应用。

Profile of perampanel and its potential in the treatment of partial onset seizures.

机构信息

Department of Functional Neurology and Epileptology and Institute for Children and Adolescent with Epilepsy, Hospices Civils de Lyon, Lyon, France ; Lyon Neuroscience Research Center, INSERM U1028/CNRS UMR 5292 Translational and Integrative Group in Epilepsy Research, Lyon, France.

出版信息

Neuropsychiatr Dis Treat. 2013;9:629-37. doi: 10.2147/NDT.S30129. Epub 2013 May 13.

Abstract

Perampanel (PER) is a novel antiepileptic compound that decreases neuronal excitability by modulating glutamatergic transmission through selective noncompetitive blockade of AMPA receptors. PER has been evaluated in three pivotal placebo-controlled randomized trials as adjunctive therapy in adult drug-resistant partial epilepsy. In comparison to placebo, adjunctive PER effectively reduces seizure frequency. The relative risk of the responder rate (95% confidence interval [CI]) was thus 1.60 (1.08-2.36), 1.79 (1.42-2.25) and 1.66 (1.24-2.23) for once-daily PER 4 mg/day, 8 mg/day and 12 mg/day, respectively. The most common adverse events associated with PER were nonspecific central nervous system side effects. Some concerns have been raised about risk of clinically significant weight gain and of psychiatric adverse events. Long-term open-label extensions of the three pivotal trials are underway. PER has recently been approved both in Europe and in the USA for the adjunctive treatment of partial onset seizures in patients aged 12 years and above. However, in the absence of a direct comparison between PER and other licensed antiepileptic drugs' efficacy and tolerability, the clinical advantages of PER over the other drugs in intractable partial epilepsy remains to be determined.

摘要

吡仑帕奈(PER)是一种新型抗癫痫化合物,通过选择性非竞争性阻断 AMPA 受体来调节谷氨酸能传递,从而降低神经元兴奋性。PER 已在三项关键性安慰剂对照随机试验中作为附加疗法在成人耐药性部分性癫痫中进行了评估。与安慰剂相比,附加 PER 可有效降低癫痫发作频率。因此,每日一次 PER 4 mg/天、8 mg/天和 12 mg/天的应答率(95%置信区间 [CI])的相对风险分别为 1.60(1.08-2.36)、1.79(1.42-2.25)和 1.66(1.24-2.23)。与 PER 相关的最常见不良事件是特异性中枢神经系统副作用。人们对 PER 引起临床显著体重增加和精神不良事件的风险提出了一些担忧。正在进行三项关键性试验的长期开放标签扩展。PER 最近已在欧洲和美国获得批准,用于治疗 12 岁及以上患者部分发作性癫痫的附加治疗。然而,由于 PER 与其他已批准的抗癫痫药物在疗效和耐受性方面没有直接比较,因此 PER 在难治性部分性癫痫中的临床优势仍有待确定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3994/3663472/72d1507bfbb8/ndt-9-629Fig1.jpg

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