【摘要】 目的:探讨盐酸二甲双胍(metformin hydrochloride,MH)普通片和缓释片在中国健康受试者中的安全性。方法:采集我科2017年11月—2018年4月开展的6项MH普通片和缓释片随机、开放、两周期、两交叉单次空腹及餐后状态下中国健康受试者人体生物等效性试验中服药受试者发生的与药物相关不良事件(correlative adverse event,CAE),比较服用普通片与缓释片、空腹与餐后、仿制药与原研药受试者发生CAE的差异。统计用SPSS 23.0软件分析。结果:本研究共纳入服药受试者269例,男199例(73.98%,199/269),(29.72±8.17)岁。试验期(17.17±8.16) d,共131例受试者发生253项不良事件(adverse event,AE),其中CAE 210项(83.00%,210/253),主要为消化道反应和实验室检查异常(95.24%,200/210),无严重不良事件(serious adverse event,SAE)发生。其中15例(5.58%,15/269)受试者中途退出试验,9例(60.00%,9/15)因为CAE退出试验。MH普通片CAE发生率高于缓释片(60.42%∶42.20%,P=0.004)、普通片CAE以消化道反应为主(71. 16%∶33.96%,χ~2=29.111,P<0.001),而缓释片以实验室检查异常为主(60.38%∶25.00%,χ~2=26. 828,P<0.001);空腹试验与餐后试验、受试制剂与参比制剂CAE发生无显著差异。结论:MH普通片和缓释片常见CAE不同,此认识有助于临床患者选择合适药物。更多还原

【Abstract】 Objective: To explore the safety of immediate release and sustained release formulations of metformin hydrochloride(MH) in Chinese healthy subjects. Methods: The correlative adverse events(CAEs) of immediate release and sustained release formulations of MH were collected from six single dose,randomized,open label,two phases,cross-over bioequivalence trials under fasting and fed conditions in Chinese healthy subjects conducted by our department between November 2017 and April 2018. The difference of CAEs between different formulations(immediate release and sustained release),different administration conditions(fasting and fed),and different drugs(generic and original tablets) were compared. Statistical analysis was performed with SPSS23. 0. Results: A total of 269 subjects were enrolled in these clinical trials,including 199 males(73. 98%,199/269) with an average age of(29. 72 ± 8. 17) y. The average trial period was(17. 17 ± 8. 16) d. A total of 253 adverse events(AEs) and 210 CAEs(83. 00%,210/253) occurred in 131 subjects,mainly including digestive tract and laboratory examination related events(95. 24%,200/210). No serious adverse events(SAE) occurred in any trial involved. 15 subjects(5. 58%,15/269) withdrew from the trials among whom 9(60. 00%,9/15) were due to CAEs. The incidence of CAEs of immediate release formulation of MH was higher than that of the sustained release formulation(60. 42% vs. 42. 20%,P = 0. 004). The CAEs of immediate release formulation of MH were mainly gastrointestinal reactions(71. 16% vs. 33. 96%,χ~2= 29. 111,P < 0. 001) and those of the sustained release formulation were abnormality of laboratory examinations(60. 38%vs. 25. 00%,χ~2= 26. 828,P<0. 001).There were no significant differences in the CAEs between fasting and fed conditions or between the generic and original formulations. Conclusion: The understanding of the fact that different formulations of MH have different CAEs is helpful for choosing suitable drugs for patients.更多还原