普拉克索片在健康人体的药动学研究及安全性评价  

Pharmacokinetics study and safety assessment of pramipexole tablets in healthy Chinese subjects

作　　者：张云轩[1,2] 陈笑艳 施孝金[1] 卢家红[4] 钟大放 钟明康[1] 

机构地区：[1]复旦大学附属华山医院药剂科,上海200040 [2]复旦大学附属华东医院药剂科,上海200040 [3]上海药物代谢研究中心,上海201203 [4]复旦大学附属华山医院神经内科,上海200040

出　　处：《复旦学报（医学版）》2015年第2期235-238,共4页Fudan University Journal of Medical Sciences

摘　　要：目的研究健康受试者口服0.125mg和0.25mg普拉克索片的药动学过程,并评价该制剂的安全性,为注册治疗不宁腿综合征(restless leg syndrome,RLS)提供药动学依据。方法采用随机、开放、双向交叉试验设计,12名健康受试者(男女各半)分两个阶段分别进行单次口服普拉克索片0.125mg和0.25mg的药动学试验,两次给药间隔13天,每次给药前及给药后采集血样,采用液相色谱-串联质谱联用法(LC-MS/MS)测定健康受试者给药后血浆中普拉克索的浓度。采用WinNonlin(R)6.0版软件计算普拉克索片的药动学参数(AUC0-t、AUC0-∞﹑ρmax﹑tmax﹑t1/2﹑CL/F等)。整个试验过程进行全面安全性评估。结果单次口服普拉克索片0.125mg和0.25mg后,ρmax分别为(237±83)μg/L和(493±155)μg/L,tmax分别为(1.71±1.64)h和(1.21±1.01)h,t1/2分别为(6.12±2.21)h和(7.27±2.17)h,AUC0-∞分别为(1 791±765)μg·h·L-1和(4 419±1 932)μg·h·L-1,不同性别的药动学参数差异无统计学意义(P>0.05).试验过程无严重不良事件发生。结论单次口服0.125mg或0.25mg普拉克索吸收很快,吸收程度随剂量增加而增加,药动学过程不受性别影响.本研究制剂安全性较好,可按试验剂量给药治疗RLS。Objective To investigate the pharmacokinetic properties and safety of a single dose of 0. 125 mg and 0. 25 mg of pramipexole tablets in healthy Chinese subjects for the registration of treating restless leg syndrome （RLS）. Methods One single-dose, open-label, randomized and crossover study of oral pramipexole tablets was conducted in 12 healthy subjects （6 males,6 females） aged from 20 to 30 years,who were orally administrated pramipexole tablet 0. 125 mg in fasted state. After a washout period of 13 days, the subjects were orally administrated another dose of 0. 25 rag. Plasma samples were collected before and after each of 12 healthy subjects was given a tablet. Concentrations of pramipexole were determined by LC-MS/MS. Pharmaeokinetic parameters （AUC0-t,AUC0-∞,tmax,t1/2,CL/F,et al） of 0. 125 mg and 0.25 mg dose groups were calculated with WinNonlin （R） Version 6. 0. Safety assessment was performed throughout the experiment. Results The main pharmacokinetic parameters of 0. 125 mg and 0.25 mg dose groups were as follows respectively：pmax, （237 ＋ 83） μg/L and （493 ＋ 155） μg/L;tmax,（1.71 ＋1.64） hand （1.21 ＋1.01） h;t1/2,（6.12 ＋2.21） h and （7.27 ＋2. 17） h;AUC0-∞ ,（1 791 ＋765） μg·h· L^-1 and （4 419＋ 1 932） μg·h· L^-1 .There was no significant difference in pharmacokinetie parameters between different gender （P ≥ 0. 05 ）. Conclusions Tablets containing （1. 125 mg and 0.25 mg pramipexole are absorbed quickly, and the extent of absorption increases with the dose. The pharmacokinetic properties are not influenced by gender. It is safe to use the agent. The experiment doses for treating RLS can be recommended.

关 键 词：普拉克索 药动学 安全性 液相色谱-串联质谱联用法(LC—MS/MS) 不宁腿综合征(RLS) 

分 类 号：R969.1[医药卫生—药理学]