恩曲他滨丙酚替诺福韦片在中国健康受试者的生物等效性研究  

Bioequivalence of emtricitabine and tenofovir alafenamide tablets in China healthy subjects

作　　者：李筱旻[1] 呼晓雷[1] 周文智 毛勇 胡伟 龚志成[1] 徐平声[1] LI Xiao-min;HU Xiao-lei;ZHOU Wen-zhi;MAO Yong;HU Wei;GONG Zhi-cheng;XU Ping-sheng(Phase I Clinical Research Unit,Xiangya Hospital,Central South University,Changsha 410008,Hunan Province,China;Chengdu Brilliant Pharmaceutical Co.,LTD.,Chengdu 610041,Sichuan Province,China;Chengdu Finelyse Pharmaceutical Technology Co.,LTD.,Chengdu 610041,Sichuan Province,China)

机构地区：[1]中南大学湘雅医院Ⅰ期临床试验研究中心,湖南长沙410008 [2]成都倍特药业股份有限公司,四川成都610041 [3]成都凡微析医药科技有限公司,四川成都610041

出　　处：《中国临床药理学杂志》2022年第1期53-59,共7页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究恩曲他滨丙酚替诺福韦片在中国健康受试者中的药代动力学特征,并评价其生物等效性。方法用随机、开放、两制剂、四周期、交叉给药的试验设计,空腹和餐后分别入组44例健康受试者,分别单次口服恩曲他滨丙酚替诺福韦片受试制剂和参比制剂225 mg,用HPLC-MS/MS法测定血浆中恩曲他滨和丙酚替诺福韦浓度,用WinNolin 7.0软件计算药代动力学参数。结果空腹组受试制剂与参比制剂恩曲他滨的主要药代动力学参数C_(max)分别为(3 251.80±757.49)和(3 363.72±848.62) ng·mL^(-1),AUC_(0-∞)分别为(13.56±2.78)和(13.73±2.67)μg·h·mL^(-1),AUC_(0-∞)分别为(13.74±2.77)和(13.90±2.67)μg·h·mL^(-1),t_(1/2)分别为(7.96±2.99)和(7.64±2.73) h;丙酚替诺福韦C_(max)分别为(233.78±110.55)和(258.38±126.07) ng·mL^(-1),AUC_(0-∞)分别为(0.14±0.06)和(0.14±0.07)μg·h·mL^(-1),AUC_(0-∞);分别为(0.14±0.06)和(0.14±0.07)μg·h·mL^(-1),t_(1/2)分别为(0.35±0.08)和(0.38±0.13) h。餐后组受试制剂与参比制剂恩曲他滨C_(max)分别为(2 902.85±584.79)和(2 948.13±640.40) ng·mL^(-1),AUC_(0-∞)分别为(12.36±1.61)和(12.60±1.66)μg·h·mL^(-1),AUC_(0-∞)分别为(12.55±1.60)和(12.78±1.65)μg·h·mL^(-1),t_(1/2)分别为(8.55±2.65)和(8.45±2.67) h;丙酚替诺福韦C_(max)分别为(262.79±130.70)和(260.59±117.76)ng·mL^(-1),AUC_(0-∞)分别为(0.25±0.10)和(0.26±0.10)μg·h·mL^(-1),AUC_(0-∞)分别为(0.25±0.10)和(0.26±0.10)μg·h·mL^(-1),t;分别为(0.40±0.10)和(0.40±0.08) h。两制剂恩曲他滨的主要药代动力学参数C_(max)、AUC_(0-∞)和AUC_(0-∞)经对数转换后进行方差分析,其90%置信区间空腹状态下分别为93.03%-102.54%,96.87%-100.53%和97.02%-100.55%;餐后状态下分别为94.94%-103.37%,97.32%-99.70%和97.37%-99.64%。丙酚替诺福韦AUC_(0-∞)和AUC_(0-∞)的90%置信区间空腹状态下分别为92.85%-104.34%和92.89%-104.36%;餐后状态下分别为92.21%-100.68%和92.25%-100.69%。�Objective To study the pharmacokinetic characteristics and bioequivalence of two emtricitabine and tenofovir alafenamide tablets in Chinese healthy subjects.Methods A randomized,open-label,two-preparation,four-period,crossover study designing was adopted in the study.A total of 44 subjects in fasting and 44 subjects in fed state received single oral dose of test(T) and reference(R) preparation of emtricitabine and tenofovir alafenamide tablets 225 mg,respectively.The concentrations of emtricitabine and tenofovir alafenamide in plasma were measured by HPLC-MS/MS.The pharmacokinetic parameters were calculated by WinNonlin 7.0 program.Results In the fasting test,the pharmacokinetic parameters of emtricitabine of T and R were as follows:C_(max)were (3 251.80±757.49) and(3 363.72±848.62) ng·mL^(-1),AUC_(0-∞)were (13.56±2.78) and (13.73±2.67)μg·h·mL^(-1),AUC_(0-∞)were(13.74±2.77) and (13.90±2.67)μg·h·mL^(-1),t_(1/2) were (7.96±2.99) and (7.64±2.73) h.The pharmacokinetic parameters of tenofovir alafenamide of T and R were as follows:C_(max)were (233.78±110.55) and(258.38±126.07) ng·mL^(-1),AUC_(0-∞)were (0.14±0.06) and (0.14±0.07)μg·h·mL^(-1),AUC_(0-∞)were(0.14±0.06) and (0.14±0.07)μg·h·mL^(-1),t_(1/2) were (0.35±0.08) and (0.38±0.13) h.In the fed test,the pharmacokinetic parameters of emtricitabine of T and R were as follows:C_(max)were (2 902.85±584.79) and(2 948.13±640.40) ng·mL^(-1),AUC_(0-∞)were (12.36±1.61) and (12.60±1.66)μg·h·mL^(-1),AUC_(0-∞)were(12.55±1.60) and (12.78±1.65)μg·h·mL^(-1),t_(1/2) were (8.55±2.65) and (8.45±2.67) h.The pharmacokinetic parameters of tenofovir alafenamide of T and R were as follows:C_(max)were (262.79±130.70) and(260.59±117.76) ng·mL^(-1),AUC_(0-∞)were (0.25±0.10) and (0.26±0.10)μg·h·mL^(-1),AUC_(0-∞)were(0.25±0.10) and (0.26±0.10)μg·h·mL^(-1),t;were (0.40±0.10) and (0.40±0.08) h.In fasting condition,the 90%confidence interval (90%CI) of C_(max),AUC_(0-∞)and AUC_(0-∞)of emtricitabine were93.03%-102.54%,9

关 键 词：恩曲他滨丙酚替诺福韦片 药代动力学 生物等效性 LC-MS/MS 

分 类 号：R978.7[医药卫生—药品]