恩格列净片在中国健康受试者体内的药代动力学及生物等效性研究

Pharmacokinetics and bioequivalence studies of empagliflozin tablets in Chinese healthy subjects

目的评价2种恩格列净片在中国健康受试者中的生物等效性和安全性。方法按单次给药、随机、开放、两周期、双交叉试验研究设计方法,空腹、餐后条件下各入组38例受试者,随机交叉单次口服恩格列净片受试制剂和参比制剂各25 mg,用HPLC-MS/MS法检测血浆中恩格列净的浓度,用Phoenix WinNonlin 7.0软件计算药代动力学参数,并进行两种制剂的生物等效性评价。结果受试者服用受试制剂和参比制剂后,空腹组血浆中恩格列净的主要药代动力学参数如下:C_(max)分别为(382.37±83.61),(358.26±71.30)ng·mL^(-1);AUC_(0-t)分别为(3359.12±559.76),(3215.68±552.68)ng·h·mL^(-1);AUC_(0-∞)分别为(3405.88±573.72),(3266.38±556.97)ng·h·mL^(-1)。餐后组血浆中恩格列净主要药代动力学参数如下:受试制剂和参比制剂的C_(max)分别为(334.89±90.15)和(315.84±91.09)ng·mL^(-1);AUC_(0-t)分别为(2768.03±485.76)和(2717.37±438.35)ng·h·mL^(-1);AUC_(0-∞)分别为(2821.59±506.26)和(2764.69±449.04)ng·h·mL^(-1)。2种制剂的C_(max)、AUC_(0-t)和AUC_(0-∞)经对数转换后90%可信区间分别为空腹状态下99.90%~112.89%,102.18%~106.95%,101.93%~106.76%;餐后状态下98.76%~113.73%,98.88%~105.23%,98.83%~105.56%。结论2种恩格列净片在中国健康受试者中具有生物等效性,安全性良好。

Objective To evaluate the bioequivalence of two kinds of empagliflozin tablets in healthy Chinese subjects.Methods This was a single-center,randomized,open-lable,single-dose,two-period,two-way crossover pharmacokinetic study.A total of 76 subjects for fasting and fed state with 38 cases in each state were given a single oral dose of test and reference preparation of empagliflozin tablet(each 25 mg).Plasma concentration of empagliflozin was measured by HPLC-MS/MS.The pharmacokinetic parameters were calculated by WinNonlin 7.0 software.Results The main pharmacokinetic parameters of empagliflozin of test and reference preparations were as follows:Under fasting state C_(max) were(382.37±83.61),(358.26±71.30)ng·mL^(-1);AUC_(0-t) were(3359.12±559.76),(3215.68±552.68)ng·h·mL^(-1);AUC_(0-∞)were(3405.88±573.72),(3266.38±556.97)ng·h·mL^(-1).Under fed state C_(max) were(334.89±90.15),(315.84±91.09)ng·mL^(-1);AUC_(0-t) were(2768.03±485.76),(2717.37±438.35)ng·h·mL^(-1);AUC_(0-∞)were(2821.59±506.26),(2764.69±449.04)ng·h·mL^(-1).The 90%confidence intervals for C_(max),AUC_(0-t) and AUC_(0-∞)of test formulation in the fasting state were 99.90%-112.89%,102.18%-106.95%,101.93%-106.76%;in the fed state were 98.76%-113.73%,98.88%-105.23%,98.83%-105.56%.Conclusion The test formulation and reference formulation of empagliflozin tablets are determined to be bioequivalent.