氯沙坦钾片在中国健康志愿者中的药动学及生物等效性试验  

Pharmacokinetics and bioequivalence of losartan potassium tablet in healthy Chinese volunteers

作　　者：冯仕银 陈卓[1] 蔡林芮[1] 邹琴[1] 苏旭[1] 郭伟一 王晶[1] 余勤 FENG Shi-yin;CHEN Zhuo;CAI Lin-rui;ZOU Qin;SU Xu;GUO Wei-yi;WANG Jing;YU Qin(Institute of Drug Clinical Trial-GCP,West China Second University Hospital,Sichuan University,Chengdu 610041,China)

机构地区：[1]四川大学华西第二医院国家药物临床试验机构,成都610041

出　　处：《中国新药杂志》2019年第10期1208-1213,共6页Chinese Journal of New Drugs

摘　　要：目的:研究氯沙坦钾在人体的药动学特征,评价在空腹和餐后条件下单次口服氯沙坦钾受试制剂与参比制剂的生物等效性。方法:采用开放、随机、三周期、部分重复交叉设计,各36名健康志愿者分别在空腹和餐后服用0.1 g氯沙坦钾受试制剂和参比制剂,采用LC-MS/MS法测定氯沙坦及其活性代谢物EXP3174的血药浓度。使用Phoenix WinNonlin 6.4版中的非房室模型分析,计算药动学参数并评价2种氯沙坦钾片空腹及餐后服用的生物等效性。结果:在空腹和餐后条件下中国健康志愿者口服受试制剂和参比制剂后的主要药动学参数(AUC_(0-∞),AUC_(0-t),C_(max))的几何均数比值90%置信区间均在80.00%～125.00%的范围内。餐后给药与空腹给药相比,T_(max)延长,C_(max),AUC_(0-t)和AUC_(0-∞)均略降低,其他药动学参数基本一致。结论:在空腹和餐后条件下氯沙坦钾受试制剂与参比制剂具有生物等效性。Objective:To study the pharmacokinetic parametersoflosartan potassium tablets in healthy Chinese volunteers,and to evaluate the bioequivalence of single oral administration of the test preparation and the reference preparation under the fasting and fed conditions.Methods:An open,randomized,three-period crossover design was performed in 36 healthy volunteers.Thirty-six healthy volunteers were given a single oral dose of 0.1 g domestic or imported losartan potassium tablet under fasting and fed conditions,respectively.Losartan and its active metabolite Exp3174 in plasma were determined by an LC-MS/MS method.By means of Phoenix WinNonlin 6.4 Software,pharmacokinetic parameters were calculated using a non-compartmental mode.The bioequivalence of domestic and imported losartan potassium tablet under the fasting and fed conditions was evaluated.Results:The 90%CIs of the geometric mean ration(GMR)of AUC0-∞,AUC0-tand Cmaxbetween the test and reference drug fell with in the limit ranges of 80.00%~125.00%under fasting and fed conditions,respectively.Postprandial administration compared with fasting administration,Tmaxprolonged,Cmax,AUC0-tand AUC0-∞were slightly lower.Other pharmacokinetic parameters are basically the same.Conclusion:The domestic losartan potassium tablets are proved to be bioequivalent to imported losartan potassium tablets both under fasting and fed conditions.

关 键 词：氯沙坦钾 空腹 餐后 液相-质谱/质谱检测法 生物等效性 

分 类 号：R927.[医药卫生—药学]