硫酸氢氯吡格雷阿司匹林片在健康志愿者中空腹及餐后生物等效性评价  

Bioequivalence of bisulfate clopidogrel aspirin tablets in healthy volunteers under fasted and fed conditions

作　　者：石蕊 郝颖翠 李艳华 张丽丽 尹文 潘静 赵可新 郭欲晓 李育巧 SHI Rui;HAO Yingcui;LI Yanhua;ZHANG Lili;YIN Wen;PAN Jing;ZHAO Kexin;GUO Yuxiao;LI Yuqiao(Phase Ⅰ Clinical Centre,Hebei Petrochina Central Hospital,Hebei Langfang 065000,China;Lepu Medical Technology(Beijing)Co.Ltd.,Beijing 102200,China)

机构地区：[1]河北中石油中心医院药物Ⅰ期临床试验研究室,河北廊坊065000 [2]乐普(北京)医疗器械股份有限公司,北京102200

出　　处：《中国医院药学杂志》2023年第21期2379-2384,共6页Chinese Journal of Hospital Pharmacy

基　　金：河北省青年科技课题(编号:20191736)。

摘　　要：目的:评价乐普药业股份有限公司首仿的硫酸氢氯吡格雷阿司匹林片(T)与赛诺菲株式会社生产的同规格药物(R)在健康志愿者中的生物等效性。方法:空腹和餐后各入组48例健康志愿者,采用单中心、单剂量、开放、随机、交叉、2制剂、4周期、2序列、全部重复的试验设计。每组志愿者每周期分别口服1片T或R,采用HPLC-MS/MS法测定血浆中氯吡格雷、阿司匹林和阿司匹林代谢物水杨酸的浓度,应用非房室模型法计算药动学参数和进行生物等效性评价。结果:空腹组46例和餐后组45例完成全部试验。对个体内变异系数>30%的药动学参数(C_(max)、AUC_(0-t)和AUC_(0-∞))采用参比制剂标度的平均生物等效性法评价,95%CI<0,两制剂间几何均值比的点估计值均在0.80~1.25。当个体内变异系数<30%时,采用平均生物等效性法评价,其几何均值比的90%CI在80.00%~125.00%。结论:T与R在健康志愿者空腹和餐后下单剂量给药时具有生物等效性,可为临床安全使用提供参考。OBJECTIVE To evaluate the bioequivalence in healthy volunteers between the first imitating bisulfate clopidogrel aspirin tablets produced by Lepu Medical Technology(Beijing)Co.Ltd.(T)and those with the same specification from Sanofi(R).METHODS This study was a single-center,single-dose,open-label,randomized,crossover,two-preparation,four-period,two-sequence,all duplicated study conducted in 48 healthy volunteers under fasted and fed conditions.Subjects were randomized to receive,in each period,a single dose of a combination tablet with T or R formulation.Plasma samples were analyzed for clopidogrel,aspirin and the aspirin metabolite salicylic acid by HPLC-MS/MS.The pharmacokinetic parameters were calculated by using non-atrioventricular model to evaluate bioequivalence.RESULTS Totally 46 and 45 volunteers respectively under the fasted and fed conditions completely finished the test.The reference-scaled average bioequivalence method was used to study the bioequivalence of C_(max),AUC_(0-t) and AUC_(0-∞)when the coefficient of variation was more than 30%,and the 95% confidence interval was less than 0,and the point estimated values of the geometric mean ratio between the 2 preparations were within the range of 0.80-1.25.The average bioequivalence method was used to evaluate when the coefficient of variation were less than 30%,and the 90% confidence intervals of geometric means were within the range of 80.00%-125.00%.CONCLUSION T and R are bioequivalent after administered at single dose under fasted and fed conditions in healthy subjects.This study can provide reliable data for clinical safe use.

关 键 词：硫酸氢氯吡格雷阿司匹林片 样本量 生物等效性 药动学 安全性 

分 类 号：R969[医药卫生—药理学]