恩替卡韦分散片的健康人体相对生物利用度及生物等效性研究

Relative bioavailability and bioequivalence of entecavir dispersible tablets in healthy Chinese male volunteers

目的:以中美上海施贵宝制药有限公司生产的恩替卡韦片(博路定)为参比制剂,研究江苏正大天晴药业股份有限公司研制的恩替卡韦分散片受试制剂的相对生物利用度,以判断两种制剂是否具有生物等效性。方法:采用随机双交叉试验设计,20例男性健康受试者禁食过夜后空腹单剂量口服恩替卡韦0.5mg,液相色谱-串联质谱法(LC-MS/MS)测定血浆中恩替卡韦的浓度,应用药物与统计(DrugAndStatistics,DAS)程序计算有关药动学参数并评价两种制剂的生物等效性。结果:单剂量口服受试制剂和参比制剂的主要药动学参数Cmax分别为(5.15±1.35)和(4.55±2.46)ng.mL-1;Tmax分别为(0.44±0.20)和(0.75±0.31)h;t1/2分别为(147±127)和(127±48)h;AUC0～96分别为(13.7±2.6)和(13.0±1.9)ng.h.mL-1;AUC0～∞分别为(27.2±13.8)和(23.3±4.5)ng.h.mL-1;相对生物利用度为(107.5±24.7)%。两制剂的AUC0～96无显著性差异,Cmax和Tmax有显著性差异。结论:两制剂吸收程度等效;与参比制剂比较,受试制剂Cmax略有提高,Tmax略有提前,体现了其分散片特征。

Objective：To study the relative bioavailability and bioequivalence of entecavir dispersible tablets （Jiangsu Chia-Tai Tianqing Pharmacy Co.Ltd.） with reference to the entecavir tablets （Baraclude,Sino-American Shanghai Squibb Pharmaceuticals Ltd.）.Methods：In a randomized crossover study,20 healthy Chinese male subjects received a single oral dose （0.5 mg） of either test or reference entecavir tablets after an overnight fast.The plasma concentrations of entecavir were determined by a validated LC-MS/MS method.The pharmacokinetic parameters,the relative bioavailability and bioequivalence of two formulations were evaluated by DAS software.Results：After a single oral dose of 0.5 mg test or reference entecavir tablets,the pharmacokinetic parameters of entecavir were as follows：Cmax（5.15±1.35） and （4.55±2.46） ng·mL-1;Tmax（0.44±0.20） and （0.75±0.31） h;t1/2（147±127） and （127±48） h;AUC0～96（13.7±2.6） and （13.0±1.9） ng·h·mL^-1;AUC0～∞（27.2±13.8） and （23.3±4.5） ng·h·mL^-1;respectively.The relative bioavailability was （107.5±24.7）%.There were significant differences in Tmax and Cmax between two tablets,but no significant difference in AUC0～96.Conclusion：The test and reference entecavir tablets are bioequivalent in absorption.The slightly increased Cmax and reduced Tmax of the test formulation are obvious exhibition of its dispersible tablet characteristics.