盐酸二甲双胍在中国健康受试者的生物等效性研究

Bioequivalence of metformin hydrochloride in Chinese healthy subjects

目的评价盐酸二甲双胍在中国健康受试者的生物等效性。方法用单剂量、随机、开放、双周期交叉试验设计。空腹及餐后状态下各24例健康受试者随机分为2组,单次口服盐酸二甲双胍受试药物与参比药物250 mg,用HPLCMS/MS法测定血浆中盐酸二甲双胍血药浓度,用Phoenix Win Nonlin 7. 0软件按非房室模型计算药代动力学参数,并进行生物等效性评价。结果空腹状态下单次口服盐酸二甲双胍受试药物与参比药物250 mg后的药代动力学参数如下:Cmax分别为(752. 83±187. 50),(736. 50±156. 28) ng·m L^(-1); AUC0-t分别为(4889. 10±839. 84)和(4892. 26±707. 40) ng·m L^(-1)·h; AUC_(0-∞)分别为(4956. 13±843. 47)和(4954. 38±717. 29) ng·m L^(-1)·h。2种制剂的C_(max)、AUC_(0-t)及AUC_(0-∞)的几何均值比值相对应的90%置信区间分别为94. 55%～109. 13%,94. 66%～104. 51%和94. 83%～104. 60%。餐后状态下单次口服盐酸二甲双胍受试药物与参比药物250 mg后的药代动力学参数如下:Cmax分别为(481. 25±109. 20)和(470. 83±88. 33) ng·m L^(-1); AUC0-t分别为(3600. 30±779. 55)和(3735. 96±976. 90) ng·m L^(-1)·h; AUC_(0-∞)分别为(3674. 02±798. 27)和(3808. 49±1008. 18) ng·m L^(-1)·h。2种药物的Cmax、AUC_(0-t)及AUC_(0-∞)的几何均值比值相对应的90%置信区间分别为96. 81%～107. 81%,92. 39%～100. 37%和92. 59%～100. 45%。结论 2种盐酸二甲双胍在中国健康受试者体内具有生物等效性。

Objective To evaluate the bioequivalence of the two metformin hydrochloride tablets in healthy subjects.Methods A single dose,randomized,open-label,two-period crossover study was conducted in healthy subjects.Twenty-four participants were administered test and reference metformin hydrochloride tablets(250 mg)in fasting and fed states respectively.The concentrations of metformin hydrochloride in plasma were determined by HPLC-MS/MS.The pharmacokinetie parameters were calculated and the bioequivalence was compared by non-compartment model of WinNonlin 7.0 program.Results After a single dose,the pharmacokinetic parameters for test and reference preparations under fasting condition were as follows:Cmax were(752.83±187.50),(736.50±156.28)ng·mL-1;AUC0-t were(4889.10±839.84),(4892.26±707.40)ng·mL-1·h;AUC0-∞were(4956.13±843.47),(4954.38±717.29)ng·mL-1·h.The 90%confidential interval(CI)of Cmax,AUC0-t and AUC0-∞of test formulation were 94.55%-109.13%,94.66%-104.51%and94.83%-104.60%.After a single dose,the pharmacokinetic parameters for test and reference preparations under fed condition were as follows:Cmaxwere(481.25±109.20),(470.83±88.33)ng·mL-1;AUC0-t were(3600.30±779.55),(3735.96±976.90)ng·mL-1·h;AUC0-∞were(3674.02±798.27),(3808.49±1008.18)ng·mL-1·h.The90%CI of Cmax,AUC0-tand AUC0-∞of tested formulation were 96.81%-107.81%,92.39%-100.37%and92.59%-100.45%.Conclusion The test and reference preparations were bioequivalence.