Shire, Wayne, PA, USA.
Shire, Lexington, MA, USA.
Neuropsychopharmacol Rep. 2020 Mar;40(1):16-29. doi: 10.1002/npr2.12082. Epub 2019 Nov 25.
To assess safety, tolerability, and pharmacokinetics of lisdexamfetamine dimesylate in Japanese and Caucasian healthy adults.
A phase 1, double-blind, randomized, placebo-controlled, single- and multiple-dose study in Japanese and Caucasian subjects. Subjects received lisdexamfetamine 20 mg or placebo on Day 1, then lisdexamfetamine 20 mg/d (Days 4-8), 50 mg/d (Days 9-13), 70 mg/d (Days 14-18), or matching placebo. Pharmacokinetic parameters for lisdexamfetamine and d-amphetamine were estimated by noncompartmental analysis.
Fifteen Japanese and 19 Caucasian subjects were enrolled and randomized. The lisdexamfetamine and d-amphetamine plasma concentration-time curves were similar for both ethnic groups following single and multiple doses. Mean area under the concentration-time curves for d-amphetamine were higher (by 11%-15%) in Japanese than Caucasian subjects following multiple dosing of lisdexamfetamine. Mean bodyweight was 17% lower in Japanese than Caucasian subjects. Weight-corrected means for oral clearance were similar in both ethnic groups, with no unexpected accumulation of d-amphetamine. Lisdexamfetamine was generally well tolerated by both ethnic groups, with no serious adverse events reported. The 10/12 Japanese and 11/16 Caucasian subjects who received lisdexamfetamine completed the study; two Japanese and three Caucasian subjects discontinued due to adverse events. Most adverse events were of mild severity.
Pharmacokinetics were generally similar for Japanese and Caucasian subjects; the minor differences observed were likely due to bodyweight differences in the two ethnic groups. Lisdexamfetamine was generally well tolerated. Adverse events were consistent with the established safety profile of lisdexamfetamine and were similar in both ethnic groups.
评估赖氨酸右旋苯丙胺甲硫酸盐在日本和白种人健康成年人中的安全性、耐受性和药代动力学。
这是一项在日本和白种人受试者中进行的、为期 1 天的、双盲、随机、安慰剂对照、单次和多次剂量的 1 期研究。受试者在第 1 天接受赖氨酸右旋苯丙胺 20mg 或安慰剂，然后在第 4-8 天接受赖氨酸右旋苯丙胺 20mg/d，第 9-13 天接受赖氨酸右旋苯丙胺 50mg/d，第 14-18 天接受赖氨酸右旋苯丙胺 70mg/d，或匹配的安慰剂。通过非房室分析估算赖氨酸右旋苯丙胺和 d-苯丙胺的药代动力学参数。
共纳入和随机分配了 15 名日本人和 19 名白种人受试者。在单剂量和多剂量给药后，两种族受试者的赖氨酸右旋苯丙胺和 d-苯丙胺血浆浓度-时间曲线相似。多剂量赖氨酸右旋苯丙胺后，日本受试者的 d-苯丙胺平均曲线下面积（AUC）较高（高 11%-15%）。日本受试者的平均体重比白种人受试者低 17%。两组受试者的口服清除率校正均值相似，d-苯丙胺无意外蓄积。两种族受试者对赖氨酸右旋苯丙胺的耐受性总体良好，均未报告严重不良事件。10/12 名日本受试者和 11/16 名白种人受试者完成了研究；2 名日本受试者和 3 名白种人受试者因不良事件而停药。大多数不良事件为轻度。
日本和白种人受试者的药代动力学总体相似；观察到的轻微差异可能归因于两种族受试者的体重差异。赖氨酸右旋苯丙胺总体耐受性良好。不良事件与赖氨酸右旋苯丙胺的既定安全性特征一致，且在两种族受试者中相似。
