Wagner M L, Landis B E
Department of Pharmacy Practice, Rutgers, State University of New Jersey, Piscataway 08855, USA.
Ann Pharmacother. 1997 Jun;31(6):738-44. doi: 10.1177/106002809703100614.
To provide a comprehensive review of riluzole, including its mechanism of action, pharmacokinetics, adverse drug reactions, drug interactions, efficacy, and administration. A brief review of amyotrophic lateral sclerosis (ALS) is also included.
A computerized search of the MEDLINE database in May 1996 was used to identify publications regarding ALS, riluzole, and metabolism by CYP1A2. Manufacturer's information on riluzole was used when there was no primary literature.
Riluzole is approximately 90% absorbed following an oral dose. Its bioavailability is 60%. Peak concentrations occur within 1-1.5 hours of administration. Riluzole extensively binds to lipoproteins and albumin. This agent primarily undergoes CYP1A2 hydroxylation and glucuronidation, after which it is eliminated by the kidneys. Clearance is reduced in native Japanese healthy subjects and may be reduced in patients with hepatic impairment. Two trials with a total of 1114 patients addressed the efficacy of riluzole in ALS. Riluzole extended the time to tracheostomy or death, and the effect was greatest with dosages of 100 mg/d or greater. No effect on patients' symptoms or global assessment was detected at 18 or 21 months. Several flaws in these trials have led to questions concerning the validity of these results. The most commonly reported adverse effects of riluzole have been transient elevation of liver enzyme concentrations (2-5 times the upper limit of normal), worsening of asthenia, nausea, vomiting, diarrhea, anorexia, dizziness, vertigo, somnolence, and mouth paresthesia. Not as commonly reported, but still very serious, is neutropenia, which occurred in 3 of 4000 patients.
Although the benefits of riluzole are questionable and it is expensive, this agent may extend the time to tracheostomy or death in patients with ALS. At present, this is the only agent approved for the treatment of ALS and should be made available for these patients.
全面综述利鲁唑，包括其作用机制、药代动力学、药物不良反应、药物相互作用、疗效及给药方法。同时简要介绍肌萎缩侧索硬化症（ALS）。
1996年5月通过计算机检索MEDLINE数据库，以查找有关ALS、利鲁唑及细胞色素P450 1A2（CYP1A2）介导代谢的文献。在无原始文献时，采用了利鲁唑生产商提供的资料。
口服利鲁唑后，约90%被吸收。其生物利用度为60%。给药后1 - 1.5小时达到血药峰浓度。利鲁唑广泛与脂蛋白和白蛋白结合。该药物主要经CYP1A2羟基化和葡萄糖醛酸化代谢，然后经肾脏排泄。在日本本土健康受试者中，其清除率降低，在肝功能损害患者中清除率可能也会降低。两项共纳入1114例患者的试验研究了利鲁唑对ALS的疗效。利鲁唑可延长行气管切开术或死亡时间，剂量为100 mg/d或更高时效果最佳。在18或21个月时，未发现对患者症状或整体评估有影响。这些试验存在的一些缺陷引发了对这些结果有效性的质疑。利鲁唑最常报告的不良反应为肝酶浓度短暂升高（为正常上限的2 - 5倍）、乏力加重、恶心、呕吐、腹泻、厌食、头晕、眩晕、嗜睡和口腔感觉异常。虽报告不那么常见但仍非常严重的是中性粒细胞减少症，4000例患者中有3例发生。
尽管利鲁唑的益处存在疑问且价格昂贵，但该药物可能会延长ALS患者行气管切开术或死亡的时间。目前，这是唯一被批准用于治疗ALS的药物，应为这些患者提供。
