富马酸丙酚替诺福韦片健康人体生物等效性评价  

Bioequivalence and safety evaluation of tenofovir alafenamide fumarate tablets in healthy volunteers

作　　者：高彩杰 郭慧娟 石景曼 刘建芬 张红蕾 GAO Caijie;GUO Huijuan;SHI Jingman(North China Pharmaceutical Huakun,Hebei Biotechnology Co.,Ltd.,Hebei Province,Shijiazhuang 050011,China)

机构地区：[1]华北制药华坤河北生物技术有限公司,石家庄市050011

出　　处：《临床合理用药杂志》2021年第8期22-24,共3页Chinese Journal of Clinical Rational Drug Use

基　　金：河北省省级科技计划资助(No:19272601D)。

摘　　要：目的评价富马酸丙酚替诺福韦片受试制剂及参比制剂在健康人体的生物等效性与安全性。方法选取符合纳入标准的参与空腹试验受试者43例与餐后试验受试者49例。依照单中心、随机、开放、单剂量空腹/餐后给药、双周期/三周期交叉试验方案,口服富马酸丙酚替诺福韦片受试制剂及参比制剂。采用液相色谱—串联质谱法测定服药后48 h内22个不同时间点的血药浓度,计算主要药动学参数。采用方差分析,双单侧t检验和90%置信区间分析进行生物等效性评价并统计不良事件发生率以进行安全性评价。结果受试制剂与参比制剂的药动学评价指标(AUC和Cmax)具有生物等效性,且安全性均较好。结论富马酸丙酚替诺福韦片受试制剂与参比制剂吸收的速度与程度基本一致,在空腹和餐后给药条件下生物等效性和安全性均良好。Objective To compare the bioequivalence and safety of tenofovir alafenamide fumarate tablets test preparation and reference preparation in healthy volunteers.Methods 43 subjects in fasting test and 49 subjects in postprandial test were selected.According to the single center,randomized,open,single dose fasting/postprandial administration,double cycle/three cycle crossover trial scheme,the subjects were arranged to take the test preparation and reference preparation of tenofovir alafenamide fumarate tablets orally.The plasma concentrations were determined by liquid chromatography tandem mass spectrometry(LC-MS/MS)at 22 different time points within 48 hours after administration,and the main pharmacokinetic parameters were calculated.Analysis of variance,double one-sided t-test and 90%confidence interval analysis were used to evaluate the bioequivalence,and the incidence of adverse events was counted for safety evaluation.Results The pharmacokinetic evaluation indexes(AUC and Cmax)of tenofovir alafenamide fumarate tablets were bioequivalent and safe.Conclusion The drug absorption rate and degree of tenofovir alfenamide fumarate tablets test preparation and reference preparation were basically the same,and showed good bioequivalence and safety under the condition of fasting and postprandial administration.

关 键 词：富马酸丙酚替诺福韦片 生物等效性 安全性 液相色谱—串联质谱法 

分 类 号：R969.1[医药卫生—药理学]