地诺孕素片在中国健康成年女性受试者空腹状态下的生物等效性研究

Bioequivalence study of dienogest tablets in Chinese healthy adult female subjects in fasting state

目的评价地诺孕素片在中国健康成年女性受试者空腹状态下的生物等效性和安全性。方法采用单中心、随机、开放、两周期、双交叉给药试验设计,首都医科大学附属北京安贞医院2022年2月21日至3月3日入选24例中国健康成年女性受试者,采用随机数字表法分为2组(参比制剂-受试制剂组和受试制剂-参比制剂组),每组12人。2组服药顺序不同,分别在第1天和第8天,先后空腹状态下服用1次参比制剂和受试制剂,或受试制剂和参比制剂(地诺孕素片2 mg)。通过采集生物样本并进行血药浓度分析,对比两药品药代动力学参数,并进行生物等效性评价,同时观察受试者的临床安全性。结果空腹口服受试制剂和参比制剂的药代动力学参数:血药峰浓度分别为(52±13)、(54±11)μg/L,达到峰浓度的时间分别为1.75(0.50,5.50)、1.00(0.50,5.50)h,从0时至t时的血药浓度-时间曲线下面积分别为(620±87)、(604±99)h·μg/L,从0时至无穷大时的血药浓度-时间曲线下面积分别为(644±97)、(628±111)h·μg/L,血浆消除半衰期分别为(9.7±1.5)、(9.8±1.8)h。主要药代动力学参数的几何均数比值均落在生物等效的80%~125%范围内。所有受试者在研究期间均未发生可能导致退出研究的不良事件和严重不良事件。结论地诺孕素片受试制剂和参比制剂在中国健康成年女性受试者空腹状态下具有生物等效性,并具有较高的安全性。

Objective To evaluate the bioequivalence and safety of dienogest tablets in Chinese healthy adult female subjects in fasting state.Methods A single center,randomized,open,two-period,double crossover trial design was designed.A total of 24 Chinese healthy adult female subjects were enrolled from February 21 to March 3,2022 in Beijing Anzhen Hospital,Capital Medical University.They were divided into two groups(reference preparation-test preparation group and test preparation-reference preparation group)by random number table method,with 12 people in each group.The two groups took the reference formulation and the test formulation,or the test formulation and the reference formulation(2 mg of denogestrel tablets)in fasting state on the 1st and 8th day,respectively.By collecting biological samples and analyzing the blood drug concentration,the pharmacokinetic parameters of the two drugs were compared,and the bioequivalence was evaluated.At the same time,the clinical safety of the subjects was observed.Results The pharmacokinetic parameters of fasting oral test preparation and reference preparation:the peak plasma concentrations were(52±13)and(54±11)μg/L,respectively,the time to peak concentrations were 1.75(0.50,5.50)and 1.00(0.50,5.50)h,respectively,area under the curve of the blood drug concentration-time from 0 to t were(620±87)and(604±99)h·μg/L,respectively,the area under the curve of the blood drug concentration-time from 0 to infinity were(644±97)and(628±111)h·μg/L,respectively,and the plasma elimination half-life were(9.7±1.5)and(9.8±1.8)h,respectively.The geometric mean ratios of the main pharmacokinetic parameters were within the bioequivalent range of 80%to 125%.During the study period,there were no adverse events leading subjects withdrawal or serious adverse events in both groups.Conclusion The test preparation and reference preparation of dienogest tablets are bioequivalent and have high safety in Chinese healthy adult female subjects under fasting state.