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

孙明利; 刘晨; 魏雅丽; 高倩; 刘茜英; 王兴河

doi:10.11665/j.issn.1000-5048.20220922001

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

1.
首都医科大学附属北京世纪坛医院，药物Ⅰ期临床试验研究室，北京 100038
2.
华润双鹤药业股份有限公司，北京 100102

基金项目: 首都医科大学附属北京世纪坛医院中心实验室开放研究课题资助项目（No.2020-KF28）

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出版历程
- 收稿日期: 2022-09-21
- 修回日期: 2023-03-02
- 刊出日期: 2023-02-24

Bioequivalence of metformin hydrochloride sustained-release tablets under fed condition in healthy subjects

1.
Phase I Clinical Trial Center, Beijing Shijitan Hospital Affiliated to Capital Medical University, Beijing 100038
2.
Resources Double-crane Pharmaceutical Co., Ltd., Beijing 100102, China

Funds: This study was supported by the Open Research Funding of Central Laboratory of BeijingShijitan Hospital Affiliated to Capital Medical University (No.2020-KF28)

摘要

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c_max、AUC_0-_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：c_max为（0.68 ± 0.14）和（0.65 ± 0.11） mg/L，AUC_0-_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c_max、AUC_0-_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。
- 盐酸二甲双胍缓释片 /
- 药代动力学 /
- 餐后 /
- 生物等效
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 c_max, AUC_0-_tand AUC_0-_∞ 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: c_max were (0.68 ± 0.14) and (0.65 ± 0.11) mg/L, AUC_0-_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.
- metformin hydrochloride sustained-release tablets /
- pharmacokinetics /
- fed /
- bioequivalent

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参考文献(14)

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