目的 評價中國健康受試者空腹和餐后狀態(tài)下單次口服鹽酸二甲雙胍緩釋片的生物等效性。方法 采用單劑量、隨機(jī)、開放、兩制劑、兩周期、交叉對照的試驗設(shè)計，健康受試者每周期在空腹或餐后狀態(tài)下口服鹽酸二甲雙胍緩釋片受試制劑和參比制劑500 mg。采用經(jīng)驗證的液相色譜-串聯(lián)質(zhì)譜（LC-MS/MS）法測定二甲雙胍的血漿濃度，使用Phoenix WinNonlin 8.0計算藥動學(xué)參數(shù)并用SAS9.4軟件進(jìn)行生物等效性評價。結(jié)果 空腹?fàn)顟B(tài)下，受試制劑和參比制劑中二甲雙胍C_max分別為（733.00±178.25）、（665.80±146.58） ng·mL^-1，AUC_0～t分別為（4 848.60±1 204.80）、（4 743.00±1 104.34） h·ng·mL^-1，AUC_{0 ～ ∞}分別為（4 940.70±1 219.48）、（4 832.58±1 093.55） h·ng·mL^-1。餐后狀態(tài)下，受試制劑和參比制劑中二甲雙胍C_max分別為（519.10±92.55）、（475.50±65.88） ng·mL^-1，AUC_0～t分別為（5 989.20±1 112.01）、（5 946.50±1 094.81） h·ng·mL^-1，AUC_{0 ～ ∞}分別為（6 052.20±1 118.35）、（6 049.80±1 062.28） h·ng·mL^-1。受試制劑和參比制劑二甲雙胍C_max、AUC_0～t和AUC_0～∞幾何均值比的90%置信區(qū)間均在80.00%～125.00%的生物等效性范圍內(nèi)。結(jié)論 鹽酸二甲雙胍緩釋片受試制劑和參比制劑在空腹和餐后狀態(tài)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

國家“重大新藥創(chuàng)制”科技重大專項（2017ZX09101001-002-044）；北京市醫(yī)院管理中心“登峰”計劃專項經(jīng)費資助項目（DFL20190803）；首都科技領(lǐng)軍人才項目（Z191100006119017）