盐酸二甲双胍缓释片健康人体生物等效性评价  

Bioequivalence of metformin hydrochloride sustained release tablets in healthy human conditions

作　　者：刘广文[1] 陈佳惠 高振月 张梦凡 李浩 杨海淼[1] LIU Guang-wen;CHEN Jia-hui;CAO Zhen-yue;ZHANG Meng-fan;LI Hao;YANG Hai-miao(PhaseⅠClinical Trial Research Ward,Afiliated Hospital to Changchun University of Chinese Medicine,Changchun 130012,China;Chia Tai Tianqing Pharmaceutical Group Co.,Ltd.,Nanjing 210000,China;Shanghai Xihua Testing Technology Service Co.,Luid.,Shanghai 201200,China)

机构地区：[1]长春中医药大学附属医院Ⅰ期临床试验研究室,长春130012 [2]正大天晴药业集团股份有限公司,南京210000 [3]上海熙华检测技术服务有限公司,上海201200

出　　处：《中国新药杂志》2021年第5期411-416,共6页Chinese Journal of New Drugs

摘　　要：目的:研究盐酸二甲双胍缓释片0.5 g·片-1在健康人体的药动学特征,并对2种制剂的生物等效性进行评价。方法:空腹/餐后各36名健康受试者口服盐酸二甲双胍缓释片受试制剂和参比制剂(Glucophage^(■)XR^(■)),采用随机、开放、两周期、两交叉空腹/餐后状态下生物等效性试验。研究采用已验证的液相色谱-串联质谱法作为测定人血浆中二甲双胍浓度的分析方法,测定服药后48 h共14个时间点的血药浓度,计算药动学参数。结果:受试者空腹状态下口服受试制剂和参比制剂后,以二甲双胍的C_(max)评价受试制剂与参比制剂的生物等效性,C_(max)的几何均值比值为101.12%,90%CI为94.68%~108.00%,个体内变异为16.36%。AUC_(0-t)的几何均值比值为100.18%,90%CI为95.13%~105.51%,个体内变异为12.85%;AUC_(0-∞)的几何均值比值为101.06%,90%CI为95.86%~106.54%,个体内变异为13.11%。受试者餐后状态下口服受试制剂和参比制剂后,C_(max)的几何均值比值为94.45%,90%CI为90.13%~98.97%,个体内变异为11.39%;以二甲双胍的AUC评价受试制剂与参比制剂的生物等效性,AUC_(0-t)的几何均值比值为103.21%,90%CI为100.27%~106.24%,个体内变异为7.04%;AUC_(0-∞)的几何均值比值为103.24%,90%CI为100.31%~106.26%,个体内变异为7.01%。结论:2种制剂在空腹/餐后状态下均具有生物等效性,液相色谱-串联质谱(LC-MS/MS)法准确快速,为临床安全用药提供理论参考。Objective:To study the pharmacokinetic characteristics of metformin hydrochloride sustainedrelease tablets (0.5 g/tablet) in healthy volunteers,and to evaluate the bioequivalence of the two preparations.Methods:A randomized,open,double-period,double-crossover trial was conducted.The tested reagent and reference reagent (Glucophage^(■)XR^(■)) for oral metformin hydrochloride sustained release tablets were applied to 36healthy subjects in fasting/fed state.In this clinical trial,the validated HPLC/tandem mass spectrometry method was used to determine the concentration of metformin in human plasma of 14 time intervals in 48 h.The pharmacokinetic parameters were calculated.Results:After the volunteers were given tested and reference preparations in fasting/fed state,bioequivalence was evaluated by C_(max)of metformin.The geometric mean ratio of C_(max)was 101.12%,the90%CI was 94.68%~108.00%,and the intra-individual variation was 16.36%.The geometric mean ratio of AUC_(0-t)was 100.18%,the 90%CI was 95.13%~105.51%,and the intra-individual variation was 12.85%.The geometric mean ratio of AUC_(0-∞) was 101.06%,90%CI was 95.86%~106.54%,and intra-individual variation was 13.11%.The geometric mean ratio of C_(max)was 94.45%,the 90%CI was 90.13%~98.97%,and the intraindividual variation was 11.39%.When the AUC of metformin was used to evaluate the bioequivalence of the tested and reference preparations,the geometric mean ratio of AUC_(0-t)was 103.21%,the 90%CI was 100.27%~106.24%,and the intra-individual variation was 7.04%.The geometric mean ratio of AUC_(0-∞)was 103.24%,90%CI was100.31%~106.26%,and intra-individual variation was 7.01%.Conclusion:Both preparations were bioequivalent in fasting/postprandial status.The liquid chromatography-tandem mass spectrometry (LC-MS/MS) used in this study was accurate,rapid,sensitive and precise,providing theoretical reference for clinical safe drug use.

关 键 词：二甲双胍 液相色谱-串联质谱法 药动学 

分 类 号：R969.4[医药卫生—药理学]