富马酸丙酚替诺福韦片在中国健康受试者体内的生物等效性研究  

Bioequivalence study of tenofovir alafenamide fumarate tablets in Chinese healthy subjects

作　　者：李晓斌[1] 汪楠[1] 胡妮娜 王宁[1] 董晨东 崔晓彤 谢荷 田妍 王文萍[1] LI Xiao-bin;WANG Nan;HU Ni-na;WANG Ning;DONG Chen-dong;CUI Xiao-tong;XIE He;TIAN Yan;WANG Wen-ping(PhaseⅠClinical Trial Ward,Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning Province,China;Innovation Drug Research Institute,China Resources Sanjiu Medical&Pharmaceutical Co.,Ltd.,Shenzhen 5181100,Guangdong Province,China;Anhui Wanbang Pharmaceuticals Techonology Co.,Ltd.,Hefei 230088,Anhui Province,China)

机构地区：[1]辽宁中医药大学附属医院Ⅰ期临床病房,辽宁沈阳110032 [2]华润三九医药股份有限公司创新药物研究院,广东深圳5181100 [3]安徽万邦医药科技股份有限公司,安徽合肥230088

出　　处：《中国临床药理学杂志》2024年第14期2113-2117,共5页The Chinese Journal of Clinical Pharmacology

基　　金：辽宁省教育厅课题基金资助项目(辽教办[2023]274号)。

摘　　要：目的评价富马酸丙酚替诺福韦片(25 mg)在中国健康受试者中的药代动力学(PK)行为,以及2种制剂的生物等效性。方法空腹试验采用单次给药、随机、开放、两周期、双交叉设计,餐后试验采用单次给药、随机、开放、三周期、部分重复交叉设计。空腹和餐后试验各入组42例健康受试者,每周期单次口服富马酸丙酚替诺福韦片受试制剂和参比制剂各25 mg。用液相色谱-串联质谱(LC-MS/MS)法检测人血浆中丙酚替诺福韦和替诺福韦的浓度,用WinNonlin软件(8.1版本)以非房室模型计算PK参数,并评价2种制剂的生物等效性,并对试验期间受试者进行相关的安全性评价。结果空腹口服受试制剂和参比制剂后,酚替诺福韦的主要PK参数:Cmax分别为(215.17±94.24)和(199.30±71.11)ng·mL^(-1),AUC_(0-t)分别为(135.44±71.60)和(123.91±53.82)h·ng·mL^(-1);替诺福韦的主要PK参数:受试制剂和参比制剂的C_(max)分别为(7.30±2.27)和(7.12±1.74)ng·mL^(-1),AUC_(0-t)分别为(186.78±60.22)和(179.44±47.44)h·ng·mL^(-1)。餐后口服受试制剂和参比制剂后,丙酚替诺福韦主要药代动力学参数:C_(max)分别为(197.69±82.19)和(197.10±110.54)ng·mL^(-1),AUC_(0-t)分别为(197.69±82.19)和(197.10±110.54)h·ng·mL^(-1);替诺福韦主要PK参数:受试制剂和参比制剂的C_(max)分别为(2.57±1.37)和(2.58±1.31)ng·mL^(-1),AUC_(0-t)分别为(227.08±74.33)和(238.51±128.30)h·ng·mL^(-1)。空腹和餐后试验受试制剂和参比制剂的C_(max)、AUC_(0-t)的几何均值比的90%置信区间均在80.00%~125.00%。空腹和餐后试验的不良事件发生率分别为21.43%和30.95%,未发生严重不良事件。结论富马酸丙酚替诺福韦片受试制剂和参比制剂具有生物等效性,且安全性良好。Objective To evaluate the pharmacokinetics(PK)of tenofovir alafenamide Fumarate tablets(25 mg)in healthy Chinese subjects after single oral administration to provide a basis for bioequivalence evaluation.Methods Using a single-dose,randomized,open-lable,two-period,two-way crossover design under fasting condition,while three-way crossover design under fed condition,42 healthy subjects respectively for fasting and fed study were enrolled,and randomized into two groups to receive a single dose of test product(T)or reference product(R)25 mg.Plasma concentration of tenofovir alafenamide and tenofovir were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.The pharmacokinetic parameters were calculated by Win Nonlin software(8.1 version)using non-compartmental model,and bioequivalence evaluation was performed for the two preparations.Relevant safety evaluations were performed during the trial.Results The test product and the reference product under fasting study,the main PK parameters of tenofovir alafenamide were as follows:C_(max)were(215.17±94.24)and(199.30±71.11)ng·mL^(-1);AUC_(0-t)were(135.44±71.60)and(123.91±53.82)h·ng·mL^(-1);the main PK parameters of tenofovir were as follows:C_(max)were(7.30±2.27)and(7.12±1.74)ng·mL^(-1),AUC_(0-t)of tenofovir were(237.16±47.09)and(230.06±43.41)h·ng·mL^(-1),respectively.The test product and the reference product under fed study,the main PK parameters of tenofovir were as follows:C_(max)were(197.69±82.19)and(197.10±110.54)ng·mL^(-1);AUC_(0-t)were(197.69±82.19)and(197.10±110.54)h·ng·mL^(-1);the main PK parameters of tenofovir were as follows:C_(max)were(2.57±1.37)and(2.58±1.31)ng·mL^(-1);AUC_(0-t)were(227.08±74.33)and(238.51±128.30)h·ng·mL^(-1),respectively.The 90%confidence interval for geometric mean ratio of C_(max),AUC_(0-t)of T and R under fed condition were between 80.00%^(-1)25.00%,respectively.The incidence of adverse events in fasting and fed tests was 21.43%and 30.95%,respectively,and no serious adverse event was rep

关 键 词：丙酚替诺福韦 替诺福韦 生物等效性 安全性 

分 类 号：R978.7[医药卫生—药品]