对恩替卡韦分散片的人体生物等效性研究

Bioequivalence of entecavir dispersible tablets in healthy volunteers

目的:比较两种恩替卡韦制剂的人体生物等效性。方法:20名健康男性志愿者随机交叉单剂量口服恩替卡韦分散片(受试制剂)与恩替卡韦片(参比制剂)0.5mg,采用LC-MS/MS法测定人血浆中恩替卡韦浓度,用BAPP2.2软件和DAS2.1软件计算药动学参数和相对生物利用度。结果:口服恩替卡韦受试制剂与参比制剂后的人体药动学参数分别为cmax(5.15±1.35)和(4.55±2.46)ng/ml,tmax(0.44±0.20)和(0.75±0.31)h,t1/2β(146.85±126.84)和(127.15±48.39)h,AUC0～24(8.38±1.61)和(8.41±1.51)ng.h.ml-1,AUC0～96(13.74±2.56)和(13.02±1.93)ng.h.ml-1,AUC0～∞(27.17±13.76)和(23.32±4.53)ng.h.ml-1。受试制剂的相对生物利用度为(107.52±24.71)%。两制剂的tmax有显著性差异(P<0.05)。受试制剂AUC0～96的90%置信区间在参比制剂的等效范围内。结论:两种恩替卡韦制剂生物利用度等效。

Objective：To investigate the bioequivalence of two entecavir preparations in healthy volunteers.Methods：A total of 20 healthy male volunteers were enrolled in a randomized cross-over study in which the subjects were randomly assigned to receive single dose of 0.5 mg entecavir dispersible tablets（test preparation）or entecavir tablet（reference preparation）.Plasma concentrations of entecavir were determined by LC-MS/MS method.The pharmacokinetic parameters and relative bioavailability were calculated with BAPP 2.2 and DAS 2.1 software.Results：The main pharmacokinetic parameters of test and reference preparations were as follows：cmax（5.15±1.35） and（4.55±2.46） ng/ml,tmax（0.44±0.20） and（0.75±0.31） h,t1/2β（146.85±126.84） and（127.15±48.39） h,AUC0-24（8.38±1.61）and（8.41±1.51） ng.h.ml-1,AUC0-96（13.74±2.56） and（13.02±1.93） ng.h.ml-1,AUC0-∞（27.17±13.76） and（23.32±4.53） ng.h.ml-1.The relative bioavailability of entecavir dispersible tablets was（107.52±24.71）%.There was significant difference in tmax between the two preparations（P0.05）.The 90% confidential intervals（CI） of AUC0-96 of the test preparation was within the bioequivalent range of the reference preparation.Conclusion：Entecavir test and reference preparations are bioequivalent.