2种恩替卡韦制剂的人体生物等效性研究

目的:研究2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空腹口服恩替卡韦胶囊(受试制剂)与恩替卡韦片(参比制剂)0.5mg后,采用液-质联用法测定人血浆中药物浓度,并用DAS2.1.1软件计算药动学参数和生物利用度。结果:恩替卡韦受试制剂与参比制剂在人体内的主要药动学参数分别为:c_(max)(4.21±1.26)、(4.06±0.80)ng·mL~(-1),t_(max)(0.6±0.4)、(0.6±0.2)h,t_(1/2β)(29.97±4.24)、(36.36±9.14)h,AUC_(0～96h)(10.84±1.80)、(10.50±1.25)ng.h.mL~(-1),AUC_(0～∞)(11.69±1.88)、(11.82±1.54)ng.h.mL~(-1)。受试制剂相对于参比制剂的生物利用度为(103.7±16.6)%。AUC_(0～96h)的90%置信区间在等效范围内。结论:2种恩替卡韦制剂为生物等效制剂。

Bioequivalence of 2 Kinds of Entecavir Preparations in Healthy Volunteers

OBJECTIVE：To study the bioequivalence of 2 kinds of entecavir preparations in human bodies.METHODS：A total of 20 healthy male volunteers were enrolled in a randomized crossover study in which the subjects were randomly assigned to receive single dose of 0.5 mg Entecavir capsule（test preparation）or Entecavir tablet（reference preparation）.The plasma concentrations of entecavir were determined by LC-MS,and the pharmacokinetic parameters and bioavailability were calculated with DAS 2.1.1 program.RESULTS：Main pharmacokinetic parameters of test preparation and reference preparation were as follows：cmax（4.21±1.26）ng·mL^-1vs.（4.06±0.80）ng·mL^-1,tmax（0.6±0.4）h vs.（0.6±0.2）h,t1/2β（29.97±4.24）h vs.（36.36±9.14）h,AUC0～96h（10.84±1.80）ng·h·mL^-1vs.（10.50±1.25）ng·h·mL^-1,AUC0～∞（11.69±1.88）ng·h·mL^-1vs.（11.82±1.54）ng·h·mL^-1.The relative bioavailability of test preparation was（103.7±16.6）%,compared with reference preparation.The 90% confidential intervals（CI）of test preparation in AUC0～96 h were among the bioequivalent range as compared with reference preparation.CONCLUSION：2 kinds of Entecavir preparations are bioequivalent.