Université d'Angers, UFR médecine, Angers cedex, F-49045 CHU d'Angers, Service Pharmacologie-Toxicologie, Angers cedex 09, France.
Br J Clin Pharmacol. 2011 Mar;71(3):403-10. doi: 10.1111/j.1365-2125.2010.03843.x.
The objective of the present study was to assess the pharmacokinetics of riluzole in patients with spinal muscular atrophy (SMA).
Fourteen patients were enrolled in an open-label, nonrandomized and repeat-dose pharmacokinetic study. All participants were assigned to receive 50mg riluzole orally for 5 days. Riluzole plasma concentrations were determined from samples obtained at day 5.
The pharmacokinetic analysis demonstrated that a dose of 50mg once a day was sufficient to obtain a daily total exposure [AUC(0,24h)=2257ng ml(-1) h] which was comparable with results obtained in adult healthy volunteers or ALS patients in whom a dose of 50mg twice a day is recommended. The pharmacokinetic simulation demonstrated that the administration of 50mg twice a day could result in higher concentrations, hence reduced safety margin.
The dose of 50mg once a day was chosen for the clinical trial evaluating the efficacy of riluzole in SMA patients.
本研究旨在评估脊髓性肌萎缩症（SMA）患者中利鲁唑的药代动力学。
14 名患者参加了一项开放标签、非随机和重复剂量的药代动力学研究。所有参与者均被分配接受 50mg 利鲁唑口服，连续 5 天。在第 5 天采集血样以测定利鲁唑的血浆浓度。
药代动力学分析表明，每天一次 50mg 的剂量足以获得每日总暴露量[AUC（0,24h）=2257ng ml(-1) h]，与在成人健康志愿者或 ALS 患者中推荐的每天两次 50mg 剂量所获得的结果相当。药代动力学模拟表明，每天两次 50mg 的给药可导致更高的浓度，从而降低了安全性。
在评估利鲁唑治疗 SMA 患者疗效的临床试验中，选择了每天一次 50mg 的剂量。
