盐酸二甲双胍缓释片在健康受试者餐后条件下的生物等效性研究
Bioequivalence of metformin hydrochloride sustained-release tablets under fed condition in healthy subjects
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摘要: 评价盐酸二甲双胍缓释片受试制剂和参比制剂在健康受试者餐后单次给药条件下的生物等效性和安全性。试验采用单中心、随机、开放、单剂量、两周期、两序列、双交叉设计，32例健康受试者在餐后状态下单次服用受试制剂或参比制剂0.5 g，在给药前（0 h）至给药后1、3、4、4.5、5、5.5、6、7、8、9、10、12、15、24、36和48 h采集静脉血4 mL，检测血浆样本中二甲双胍的浓度，用Win Nonlin 7.0 软件计算药代动力学参数，当受试制剂与参比制剂的cmax、AUC0-t、AUC0-∞几何均值比的90%置信区间均在80.00% ~ 125.00%等效区间内，证明两制剂生物等效。有1例受试者因不良事件脱落。受试制剂和参比制剂的主要药代动力学参数：cmax为（0.68 ± 0.14）和（0.65 ± 0.11） mg/L，AUC0-t为（7.33 ± 1.65）和（7.00 ± 1.89） h·mg/L，AUC0-∞为（7.39 ± 1.67）和（7.06 ± 1.91） h·mg/L；二者cmax、AUC0-t和AUC0-∞几何均值比的90%置信区间分别为101.45% ~ 109.14%、100.08% ~ 112.32%和100.24% ~ 112.28%，均在80.00% ~ 125.00%生物等效区间内。试验过程中无严重不良事件和非预期不良事件发生。结果表明，盐酸二甲双胍缓释片受试制剂和参比制剂在健康受试者中餐后单次给药条件下生物等效，二者安全性和耐受性好。Abstract: To evaluate bioequivalence and safety of two kinds of metformin hydrochloride sustained-release tablets (test preparation vs reference preparation) under the condition of fed and single administration.A single center, randomized, open, single-dose, two-period, two-sequence, and double-crossover design was used.32 healthy subjects took 0.5 g of test preparation or reference preparation under fed and single-dose administration.4 mL of venous blood was collected from before administration (0 h) to 1, 3, 4, 4.5, 5, 5.5, 6, 7, 8, 9, 10, 12, 15, 24, 36 and 48 h after administration.The concentration of metformin in plasma samples was detected, and then the pharmacokinetic parameters were calculated by WinNonlin 7.0 software.When the 90% confidence intervals of cmax, AUC0-t and AUC0-∞ geometric mean ratio of test preparation and reference preparation were within 80.00%-125.00% equivalent intervals respectively, the bioequivalence of the two preparations was proved.One subject fell off due to adverse events.The main pharmacokinetic parameters of test preparation and reference preparation as follows: cmax were (0.68 ± 0.14) and (0.65 ± 0.11) mg/L, AUC0-t were (7.33 ± 1.65) and (7.00 ± 1.89) h·mg/L, AUC0-∞ were (7.39 ± 1.67) and (7.06 ± 1.91) h·mg/L, respectively.The 90% confidence intervals of the geometric mean ratio of the two main pharmacokinetic parameters were 101.45%-109.14%, 100.08%-112.32% and 100.24%-112.28%, respectively, which fell within the bioequivalence interval of 80.00%-125.00%.There were no serious adverse events and unexpected adverse events during the trial.The results show that test preparation and reference preparation are bioequivalent under fed and single-dose administration, safe and well tolerated in healthy subjects.
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