盐酸二甲双胍缓释片在健康人体的生物等效性研究

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，Cmax分别为（700.6±191.1）和（694.5±169.2）ng/mL，AUC0-t分别为（4 858.7±1 134.3）和（4 809.3±1 188.6）ng·h·mL-1，AUC0-∞分别为（5 010.9±1 114.5）和（4 962.5±1 184.1）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Cmax分别为（738.4±121.9）和（738.0±128.7）ng/mL，AUC0-t分别为（7 558.3±1 271.8）和（7 761.5±1 486.0）ng·h·mL-1，AUC0-∞分别为（7 713.7±1 275.5）和（7 924.3±1 506.3）ng·h·mL-1。空腹试验二甲双胍受试制剂/参比制剂Cmax、AUC0-t和AUC0-∞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Cmax、AUC0-t、AUC0-∞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。

Bioequivalence of metformin hydrochloride sustained-release tablets in healthy subjects

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: Cmax were (700.6±191.1) and (694.5±169.2) ng/mL, AUC0-t were (4 858.7±1134.3) and (4 809.3±1 188.6) ng·h·mL-1, AUC0-∞ were (5 010.9±1 114.5) and (4 962.5±1 184.1) ng·h·mL-1. In the fed test, the pharmacokinetic parameters of T and R were as follow: Cmax were (738.4±121.9) and (738.0±128.7) ng/mL, AUC0-t were (7 558.3±1 271.8) and (7 761.5±1 486.0) ng·h·mL-1, AUC0-∞ were (7 713.7±1 275.5) and (7 924.3±1 506.30) ng·h·mL-1. In fasting condition, the 90% confidence interval (90%CI) of Cmax, AUC0-t and AUC0-∞ of metformin were 92.16%-111.56%, 93.36%-110.93% and 93.58%-110.39%. In fed condition, the 90%CI of Cmax, AUC0-t and AUC0-∞ 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.