盐酸二甲双胍缓释片在健康人体的生物等效性研究  

Bioequivalence of metformin hydrochloride sustained-release tablets in healthy subjects

作　　者：李筱旻[1] 金浩 周文智 杨汉跃 邹婷[1] 郭洁 徐平声[1] LI Xiaomin;JIN Hao;ZHOU Wenzhi;YANG Hanyue;ZOU Ting;GUO Jie;XU Pingsheng(Phase I Clinical Research Unit,Xiangya Hospital,Central South University,Changsha 410008,Hunan,China;Jiangsu Deyuan Pharmaceutical Co.,Ltd,Lianyungang 222000,Jiangsu,China)

机构地区：[1]中南大学湘雅医院Ⅰ期临床试验研究中心,湖南长沙410008 [2]江苏德源药业股份有限公司,江苏连云港222000

出　　处：《中国临床药理学与治疗学》2021年第4期408-413,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家科技重大专项(重大新药创制)(2017ZX09304014)。

摘　　要：目的:研究2种盐酸二甲双胍缓释片在中国健康受试者中的生物等效性。方法:采用随机、开放、两周期、交叉设计,空腹试验36名、餐后试验23名健康受试者单次口服盐酸二甲双胍缓释片(0.5 g)试验制剂(T)与参比制剂(R),采用液相色谱-串联质谱(LC-MS/MS)法测定血浆中二甲双胍的血药浓度,应用WinNonlin 7.0软件计算药动学参数,SAS9.4软件进行统计分析。结果:空腹试验中试验制剂与参比制剂中二甲双胍的主要药动学参数,C_(max)分别为(700.6±191.1)和(694.5±169.2)ng/mL,AUC_(0-t)分别为(4858.7±1134.3)和(4809.3±1188.6)ng·h·mL^(-1),AUC_(0-∞)分别为(5010.9±1114.5)和(4962.5±1184.1)ng·h·mL^(-1)。餐后试验中试验制剂与参比制剂中二甲双胍的主要药动学参数C max分别为(738.4±121.9)和(738.0±128.7)ng/mL,AUC_(0-t)分别为(7558.3±1271.8)和(7761.5±1486.0)ng·h·mL^(-1),AUC_(0-∞)分别为(7713.7±1275.5)和(7924.3±1506.3)ng·h·mL^(-1)。空腹试验二甲双胍受试制剂/参比制剂C max、AUC_(0-t)和AUC_(0-∞)几何均数的比值(GMR)分别为101.40%、101.77%、101.64%,其90%置信区间(90%CI)分别为92.16%~111.56%、93.36%~110.93%、93.58%~110.39%;餐后试验二甲双胍受试制剂/参比制剂C max、AUC_(0-t)、AUC_(0-∞)的GMR分别为100.83%、98.27%和98.28%,其90%CI分别为96.74%~105.10%,94.94%~101.71%,95.00%~101.68%。均完全落在80.00%~125.00%之间。结论:两种盐酸二甲双胍缓释片剂具有生物等效性。AIM:To study the bioequivalence of two metformin hydrochloride sustained-release tablets in Chinese healthy subjects.METHODS:A randomized,open-label,two-period,crossover study design was adopted in the study.In fasting test 36 and in fed test 23 healthy subjects were given a single oral dose of metformin hydrochloride sustained-release tablet(0.5 g).The concentration of metformin in plasma was measured by HPLC-MS/MS.The pharmacokinetic parameters were calculated by WinNonlin 7.0 program,and statistical analysis were performed by using SAS9.4 statistics software.RESULTS:In the fasting test,the pharmacokinetic parameters of metformin of the test(T)and reference(R)preparation were as follow:C max were(700.6±191.1)and(694.5±169.2)ng/mL,AUC_(0-t)were(4858.7±1134.3)and(4809.3±1188.6)ng·h·mL^(-1),AUC_(0-∞)were(5010.9±1114.5)and(4962.5±1184.1)ng·h·mL^(-1).In the fed test,the pharmacokinetic parameters of T and R were as follow:C max were(738.4±121.9)and(738.0±128.7)ng/mL,AUC_(0-t)were(7558.3±1271.8)and(7761.5±1486.0)ng·h·mL^(-1),AUC_(0-∞)were(7713.7±1275.5)and(7924.3±1506.30)ng·h·mL^(-1).In fasting condition,the 90%confidence interval(90%CI)of C max,AUC_(0-t)and AUC_(0-∞)of metformin were 92.16%-111.56%,93.36%-110.93%and 93.58%-110.39%.In fed condition,the 90%CI of C max,AUC_(0-t)and AUC_(0-∞)of metformin were 96.74%-105.10%,94.94%-101.71%and 95.00%-101.68%.All datas were in the area of 80.00%-125.00%.CONCLUSION:The two metformin hydrochloride sustained-release tablets were bioequivalent.

关 键 词：盐酸二甲双胍缓释片 生物等效性 药物动力学 

分 类 号：R969[医药卫生—药理学]