富马酸替诺福韦酯胶囊在健康人体内的药动学研究

Study on pharmacokinetics of tenofovir disoproxil fumarate capsules in healthy volunteers

目的:建立测定人血浆中替诺福韦浓度的液相色谱-质谱-质谱(LC-MS-MS)联用方法,研究富马酸替诺福韦酯胶囊在健康人体内的药动学。方法:9名健康志愿受试者单剂量口服300 mg富马酸替诺福韦酯胶囊,采用LC-MS-MS联用法测定给药后不同时间点血药浓度,计算其药动学参数。结果:富马酸替诺福韦酯胶囊在健康人体内的主要药动学参数为:t1/2(15.67±2.70)h,cmax(273.00±67.48)μg/L,tmax(2.83±1.00)h,AUC0→48(2 516.94±451.26)ng.h.mL-1,CL(1.70±0.33)L.h-1.kg-1,MRT0→48(14.60±1.34)h(n=9)。结论:该方法灵敏度高、专属性强、准确、简便,适用于富马酸替诺福韦酯胶囊的人体药动学研究。

Objective： To establish a LC-MS-MS method for determination of plasma concentration of tenofovir disoproxil fumarate and to study its pharmacokinetics in healthy human body. Methods：Nine healthy volunteers were given single dose of tenofovir disoproxil fumarate capsules（300 mg） orally. The plasma concentrations at different time after oral administration of tenofovir disoproxil fumarate were determined by LC-MS-MS method and the main pharmacokinetic parameters were calculat- ed. Results：The main pharmacokinetic parameters of tenofovir disoproxil fumarate capsules in healthy volunteers were as fol- lows.t1/2 （15.67±2.70） h,cmax（273. 00±67. 48）μg/L,tmax（2. 83±1. 00） h,AUC0-48 （2 516.94±451.26） ng·h·mL^-1 ,CL （1.70±0.33） L · h^-1 · kg^-1 ,MRT0-48 （14.60 ±1.34） h（n = 9）. Conclusion： This method is sensitive, specific, accurate and simple. It is suitable to be used in research on pharmacokinetics of tenofovir disoproxil fumarate in human body.