盐酸二甲双胍片在成年健康受试者中空腹单次给药条件下的生物等效性研究

Bioequivalence of metformin hydrochloride tablets under fasting and single-dose conditions in adult healthy volunteers

目的评价健康受试者在空腹单次给药条件下服用2种盐酸二甲双胍片的生物等效性和安全性。方法按单中心、开放、随机、单剂量、两周期、两序列、双交叉设计。36例成年健康受试者单剂量空腹口服盐酸二甲双胍片受试制剂或参比制剂850 mg,用液相色谱-质谱法测定血浆中二甲双胍血药浓度,用WinNonlin 7.0软件计算药代动力学参数。结果试验过程中有4例受试者因不良事件脱落。受试制剂和参比制剂盐酸二甲双胍片的主要药代动力学参数:C_(max)分别为(1 779.38±467.17)和(1 814.12±503.99)ng·mL^(-1),AUC_(0-t)分别为(1.06×10^(4)±2 584.94)和(1.09×10^(4)±2 872.52)ng·mL^(-1)·h;AUC_(0-∞)分别为(1.07×10^(4)±2 567.83)和(1.11×10^(4)±2 865.94)ng·mL^(-1)·h。受试制剂与参比制剂C_(max)、AUC_(0-t)和AUC_(0-∞)几何均值比的90%置信区间均落在80.00%~125.00%。试验过程中无严重不良事件和非预期不良事件发生。结论 2种盐酸二甲双胍片在成年健康受试者中在空腹单次给药条件下具有生物等效性,且安全性较好。

Objective To evaluate the bioequivalence and safety of two kinds of metformin hydrochloride tablets administration under fasting and single-dose conditions in healthy adult volunteers. Methods A trial with single center, open, randomized, single-dose of test preparation or reference preparation of metformin hydrochloride tablets(850 mg), two cycles, two sequences, double crossover design was performed under fasting conditions in 36 healthy adult volunteers. The plasma concentration of metformin was determined by liquid chromatography-mass spectrometry. The pharmacokinetic parameters were calculated by WinNonlin 7.0 software to determine whether the two preparations were equivalent. The drug-related adverse events were compared between the test preparation and the reference preparation. Results During the trial, 4 subjects fell off due to adverse events. Main pharmacokinetic parameters of metformin hydrochloride tablets, including test preparation and reference preparation: C_(max) were(1 779.38±467.17) and(1 814.12±503.99)ng·mL^(-1), AUC_(0→t) were(1.06×10^(4)±2 584.94) and(1.09×10^(4)±2 872.52) ng·mL^(-1)·h, AUC_(0→∝) were(1.07×10^(4)±2 567.83) and(1.11×10^(4)±2 865.94) ng·mL^(-1)·h.The 90% confidence intervals of C_(max),AUC_(0→t),AUC_(0→∞) geometric mean ratio between the test preparation and the reference preparation were all in the range of 80.00%-125.00%. There were no serious adverse events and unexpected adverse events during the trial. Conclusion Two brands of metformin hydrochloride tablets are bioequivalent in healthy adult volunteers under the fasting and single-dose conditions. Test preparation and reference preparation are safe and have no significant difference.