盐酸二甲双胍片在中国健康受试者中的生物等效性研究

目的研究盐酸二甲双胍片在中国健康受试者中的药代动力学特征,并评价其生物等效性。方法空腹和餐后分别入组24例健康受试者,采用随机、开放、单次给药、两周期、两制剂、两序列交叉试验设计,受试者单次口服盐酸二甲双胍片受试药物或参比药物0.25 g,采用液质联用法(LC-MS/MS)测定血浆中二甲双胍浓度,计算主要药代动力学参数,评价受试药物与参比药物的生物等效性。结果单次空腹给药受试药物与参比药物盐酸二甲双胍片的主要药代动力学参数:C_max分别为(766.00±280.00)和(784.00±249.00)ng·mL^-1;t_max分别为2.50(1.00,4.00)h和2.50(1.00,4.00)h;t_1/2分别为(3.67±0.92)和(3.39±0.92)h;AUC_0-t分别为(4910.00±1770.00)和(4980.00±1610.00)h·ng·mL^-1;AUC_0-∞分别为(5000.00±1750.00)和(5090.00±1610.00)h·ng·mL^-1。单次餐后给药受试药物与参比药物盐酸二甲双胍片的主要药代动力学参数:C_max分别为(496.00±91.50)和(482.00±56.60)ng·mL^-1;t_max分别为3.50(1.50,4.00)h和4.00(1.00,4.00)h;t_1/2分别为(3.46±0.82)和(3.50±0.77)h;AUC_0-t分别为(3710.00±623.00)和(3660.00±611.00)h·ng·mL^-1;AUC_0-∞分别为(3840.00±624.00)和(3760.00±582.00)h·ng mL^-1。两药物的主要药代动力学参数C_max、AUC_0-t、AUC_0-∞几何均值的比值及其90%置信区间空腹状态下分别为93.90%(85.30%~103.37%),95.05%(87.61%~102.98%)和93.90%(88.24%~102.40%);餐后状态下分别为102.39%(97.67%~107.33%),101.79%(96.22%~107.69%)和102.37%(97.30%~107.70%)。结论在空腹和餐后状态下,两种盐酸二甲双胍片的主要药代动力学参数相近,吸收速度和程度均一致,两制剂生物等效,同时两制剂在中国健康受试人群中具有相似的安全性和耐受性。

Bioequivalence of metformin hydrochloride tablets in healthy Chinese subjects

Objective To study the pharmacokinetic characteristics of metformin tablets in healthy Chinese subjects under fasting and fed conditions and evaluate its bioequivalence.Methods 24 healthy subjects were enrolled under fasting and fed conditions,and a random,open,single-dose,two preparations,two sequences and double-crossover design was used to give the test or reference preparations 0.25 g under fasting and postprandial conditions.The concentration of metformin in plasma was detected by LC-MS/MS,and the main pharmacokinetic parameters were calculated to evaluate the bioequivalence.Results The main pharmacokinetic parameters of the tested and reference preparations were as follows:the fasting condition C_maxwere(766.00±280.00)and(784.00±249.00)ng·mL^-1;t_maxwere 2.50(1.00,4.00)h and 2.50(1.00,4.00)h;t_1/2were(3.67±0.92)and(3.39±0.92)h;AUC_0-twere(4910.00±1770.00)and(4980.00±1610.00)h·ng·mL^-1;AUC_0-∞were(5000.00±1750.00)and(5090.00±1610.00)h·ng·mL^-1.The fed condition C_maxwere(496.00±91.50)and(482.00±56.60)ng·mL^-1;t_maxwere 3.50(1.50,4.00)h and 4.00(1.00,4.00)h;t_1/2were(3.46±0.82)and(3.50±0.77)h;AUC_0-twere(3710.00±623.00)and(3660.00±611.00)h·ng·mL^-1;AUC_0-∞were(3840.00±624.00)and(3760.00±582.00)h·ng·mL^-1.The ratio of geometric mean and its 90%confidence interval of C_max,AUC_0-t,and AUC_0-∞in fasting condition were 93.90%(85.30%-103.37%),95.05%(87.61%-102.98%)and 93.90%(88.24%-102.40%).In fed condition,the ratio of geometric mean and its 90%confidence interval were 102.39%(97.67%-107.33%),101.79%(96.22%-107.69%)and 102.37%(97.30%-107.70%).Conclusion Two kinds of metformin hydrochloride tablets are bioequivalent,and have similar safety and tolerability in healthy Chinese subjects.