盐酸二甲双胍缓释片(Ⅲ)在中国健康受试者中的生物等效性研究  

Bioequivalency study of metformin hydrochloride sustained-release tablets(Ⅲ)in Chinese healthy subjects

作　　者：邵一珉 姚军[1] 李君[1] 王碧坤 徐文振 徐英 张俊清[1] SHAO Yi-min;YAO Jun;LI Jun;WANG Bi-kun;XU Wen-zhen;XU Ying;ZHANG Jun-qing(Department of Endocrinology,Peking University First Hospital,Beijing 100034,China;Zhongchuang Huiming(Beijing)Pharmaceutical Technology Co.,Ltd.,Beijing 101500,China;Qingdao Baiyang Pharmaceutical Co.,Ltd.,Qingdao 266042,Shandong Province,China)

机构地区：[1]北京大学第一医院内分泌科,北京100034 [2]中创慧铭(北京)医药科技有限公司,北京101500 [3]青岛百洋医药股份有限公司,山东青岛266042

出　　处：《中国临床药理学杂志》2024年第23期3444-3448,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的评价盐酸二甲双胍缓释片(Ⅲ)单次给药与盐酸二甲双胍片2次给药在健康受试者中的生物等效性。方法用双周期、开放、自身交叉对照试验设计,10例健康受试者首先接受受试制剂[盐酸二甲双胍缓释片(Ⅲ)]2.0 g顿服,经过7 d洗脱期后,再接受参比制剂(盐酸二甲双胍片)1.0 g,每日2次,口服。用液相色谱联用质谱(LC-MS/MS)法测定服药后不同时间点血浆中二甲双胍的浓度,通过Analyst 1.6.3软件计算药代动力学参数,并对2种药物进行生物等效性评价。用双单侧t检验、计算90%置信区间评价等效性,次要参数tmax用非参数检验的统计分析方法来评价等效性。结果受试制剂与参比制剂的药代动力学参数:AUC_(0-24 h)分别为(16.43±4.46)和(18.69±4.68)μg·h·mL^(-1),AUC_(INF_obs)分别为(17.60±4.56)和(20.09±5.78)μg·h·mL^(-1),C_(max)分别为(1893.97±585.88)和(1437.35±281.21)ng·mL^(-1),t_(max)分别为(7.60±1.58)和(4.70±2.41)h,t_(1/2)分别为(10.95±2.58)和(3.33±0.62)h。结论盐酸二甲双胍缓释片(Ⅲ)单次给药在中国健康受试者体内达峰时间和半衰期较盐酸盐酸二甲双胍片延长,生物等效性与盐酸二甲双胍片2次给药相当。Objective To evaluate the bioequivalency of single administration of metformin hydrochloride sustained-release tablets(Ⅲ)and double administration of metformin hydrochloride tablet by self-cross test in healthy subjects.Methods A two-cycle,open,self-controlled cross-control trial was conducted in which 10 cases healthy subjects first received test prepatration metformin hydrochloride sustained-release tablet(Ⅲ)2.0 g and then received reference preparation(metformin hydrochloride tablet)1.0 g twice daily after a 7-day washout period.The plasma concentrations of metformin at different time points after administration were measured by liquid chromatography tandem mass spectrometry(LC-MS/MS).The pharmacokinetic parameters were calculated by Analyst 1.6.3,and the bioequivalency of the two drugs was evaluated.A double unilateral t-test and 90%confidence interval were used to assess the equivalence.A non-parametric test statistical analysis was used to evaluate the equivalence of the secondary parameter tmax.Results The pharmacokinetic parameters of test prepatration and reference preparation were AUC_(0-24 h) were(16.43±4.46)and(18.69±4.68)μg·h·mL^(-1),AUC_(INF_obs) were(17.60±4.56)and(20.09±5.78)μg·h·mL^(-1),C_(max) were(1893.97±585.88)and(1437.35±281.21)ng·mL^(-1),t_(max) were(7.60±1.58)and(4.70±2.41)h;t_(1/2) were(10.95±2.58)and(3.33±0.62)h.Conclusion The peak time and half-life of metformin hydrochloride sustained-release tablet(Ⅲ)after single administration in Chinese healthy subjects are longer than that of metformin hydrochloride tablet,and the bioequivalency is comparable to that of metformin hydrochloride tablet after two administration.

关 键 词：盐酸二甲双胍缓释片(Ⅲ) 生物等效性 药代动力学 健康受试者 

分 类 号：R977.15[医药卫生—药品]