目的 评价中国健康受试者空腹和餐后状态下单次口服盐酸二甲双胍缓释片的生物等效性。方法 采用单剂量、随机、开放、两制剂、两周期、交叉对照的试验设计，健康受试者每周期在空腹或餐后状态下口服盐酸二甲双胍缓释片受试制剂和参比制剂500 mg。采用经验证的液相色谱-串联质谱（LC-MS/MS）法测定二甲双胍的血浆浓度，使用Phoenix WinNonlin 8.0计算药动学参数并用SAS9.4软件进行生物等效性评价。结果 空腹状态下，受试制剂和参比制剂中二甲双胍C_max分别为（733.00±178.25）、（665.80±146.58） ng·mL^-1，AUC_0～t分别为（4 848.60±1 204.80）、（4 743.00±1 104.34） h·ng·mL^-1，AUC_{0 ～ ∞}分别为（4 940.70±1 219.48）、（4 832.58±1 093.55） h·ng·mL^-1。餐后状态下，受试制剂和参比制剂中二甲双胍C_max分别为（519.10±92.55）、（475.50±65.88） ng·mL^-1，AUC_0～t分别为（5 989.20±1 112.01）、（5 946.50±1 094.81） h·ng·mL^-1，AUC_{0 ～ ∞}分别为（6 052.20±1 118.35）、（6 049.80±1 062.28） h·ng·mL^-1。受试制剂和参比制剂二甲双胍C_max、AUC_0～t和AUC_0～∞几何均值比的90%置信区间均在80.00%～125.00%的生物等效性范围内。结论 盐酸二甲双胍缓释片受试制剂和参比制剂在空腹和餐后状态下均具有生物等效性。

Objective To evaluate the pharmacokinetics and bioequivalence of Metformin Hydrochloride Extended-Release Tablets under fasting and fed conditions in Chinese healthy subjects. Methods This was a randomized, open-label, double-sequence, twoperiod, crossover designed study, and healthy subjects enrolled and administrated a single dose of 500 mg test and reference Metformin Hydrochloride Extended-Release Tablets in each period under fasting or fed condition. The plasma concentrations of metformin were determined by a validated LC-MS/MS method. The pharmacokinetic parameters were calculated with WinNonlin 8.0 and the bioequivalence was evaluated through SAS 9.4 software. Results In the fasting condition, the major pharmacokinetic parameters of metformin of test and reference formulations were as follows, C_max were (733.0 ±178.25) and (665.8 ±146.58) ng·mL^-1, AUC _0-t were (4 848.60 ±1 204.80) and (4 743.00 ±1 104.34) h·ng·mL^-1, AUC_0-∞ were (4 940.70 ±1 219.48) and (4 832.60 ±1 093.55) h·ng·mL^-1, respectively. Subjects administrated test and reference formulations in fed condition had C_max of (519.10 ±92.55) and (475.50 ±65.88) ng·mL^-1,AUC_0-tof (5 989.20 ±1 112.01) and (5 946.50 ±1 094.81) h·ng·mL^-1,AUC_0-∞of (6 052.20 ±1 118.35) and (6 049.80 ±1 062.28) h·ng·mL^-1, respectively. The 90% confidence intervals of geometric mean ratios were all within the bioequivalence range of 80.00%-125.00%. Conclusion The test formulation of Metformin Hydrochloride Extended-Release Tablets was bioequivalent to the reference product both under fasting and fed conditions.

R969.1

国家“重大新药创制”科技重大专项（2017ZX09101001-002-044）；北京市医院管理中心“登峰”计划专项经费资助项目（DFL20190803）；首都科技领军人才项目（Z191100006119017）