Abstract：
This randomized, parallel-group study evaluated the plasma pharmacokinetic profile of safinamide in 24 healthy Chinese men and women, randomly assigned to receive 50 or 100 mg of safinamide as a single dose, followed, after a 7-day washout, by multiple doses once daily for 7 days. Plasma safinamide was determined up to 96 h after the first single dose (day 1) and the last multiple dose (day 14), and up to 24 h after the first multiple dose (day 8). Following single- and multiple-dose administration, peak concentrations were achieved at a median time of 1.5-2 h. Plasma exposure increased in a dose-proportional manner. After single dose, mean half-life was 23-24 h. Area under the concentration-time curve (AUC) from time zero extrapolated to infinity was only slightly higher than AUC from time zero to the last quantifiable concentration, corresponding for the 2 parameters, respectively, to 12,380 and 11,560 ng • h/mL for the 50 mg and to 22,030 and 20,790 ng • h/mL for the 100-mg dose. AUC in the dosing interval at steady state was 13,150 and 23,100 ng • h/mL for 50 and 100 mg of safinamide. Steady state was reached in 6 days, accumulation was approximately twofold, and the pharmacokinetics were time independent. The plasma safinamide pharmacokinetic profile observed in this study is in line with the published results in both Chinese and non-Asian populations.
摘要：
这个随机的，平行组研究评估了沙芬酰胺在24名健康中国男性和女性中的血浆药代动力学特征，随机分配接受50或100毫克的沙芬酰胺作为单剂量，跟着，经过7天的清洗，多剂量，每日一次，持续7天。在第一次单剂量（第1天）和最后一次多剂量（第14天）后的96小时内测定血浆沙芬酰胺，并在第一次多次给药后24小时（第8天）。单剂量和多剂量给药后，在1.5-2小时的中值时间达到峰值浓度。血浆暴露以剂量成比例的方式增加。单剂量后，平均半衰期为23-24小时。从时间零外推至无穷大的浓度-时间曲线下面积（AUC）仅略高于从时间零到最后可量化浓度的AUC，对应于2个参数，分别,对于50mg剂量为12,380和11,560ng•h/mL，对于100mg剂量为22,030和20,790ng•h/mL。对于50和100mg的safinamide,在稳态的给药间隔中的AUC为13,150和23,100ng·h/mL。6天达到稳定状态,积累大约是两倍，药代动力学与时间无关。在这项研究中观察到的血浆沙芬酰胺药代动力学特征与在中国和非亚洲人群中发表的结果一致。
