中国西部健康人群口服替诺福韦富马酸酯片的药动学研究  

Pharmacokinetics of Tenofovir Disoproxil Fumarate Tablets in Healthy Volunteers from Western China

作　　者：谭瑞[1] 杨俊卿[1] 颜波[2] 尚京川[2] 黄爱龙[3] 

机构地区：[1]重庆医科大学药理学教研室,重庆市400016 [2]重庆医科大学药物分析教研室,重庆市400016 [3]重庆医科大学感染性疾病分子生物学教育部重点实验室,重庆市400016

出　　处：《中国药房》2011年第22期2048-2050,共3页China Pharmacy

基　　金：“艾滋病和病毒性肝炎等重大传染病防治”科技重大专项“十一五”计划(2008ZX10001-016)

摘　　要：目的:研究口服替诺福韦富马酸酯片在中国西部健康人群的药动学特征。方法:24名健康志愿者随机分为3组,每组8人,分别给予替诺福韦富马酸酯片300mg、恩曲他滨胶囊200mg+替诺福韦富马酸酯片300mg、脂肪食物(食物中脂肪比例50%)+替诺福韦富马酸酯片300mg,分别在服药前0h及服药后0.5、0.75、1、1.5、2、3、4、6、8、12、24、36、48、72h时取静脉血2mL,分离血浆,采用固相萃取,以高效液相色谱-紫外(HPLC-UV)法测定替诺福韦血药浓度,以DAS(Ver2.1.1)软件计算药动学参数。结果:3组药动学参数分别为:t1/(218.78±3.28)、(12.72±2.83)、(13.08±1.47)h,tma(x1.05±0.16)、(1.28±0.30)、(1.55±0.37)h,cma(x290.71±63.21)、(420.84±96.71)、(429.06±174.81)ng·mL-1,AUC0～7(21871.60±377.00)、(3869.42±962.85)、(3569.47±633.47)μg·h·L-1,AUC0～∞(2284.16±373.54)、(4107.09±974.82)、(3856.00±618.39)μg·h·L-1,CL/F(2.25±0.39)、(1.28±0.28)、(1.33±0.20)L·h-1·kg-1。与替诺福韦富马酸酯组比较,恩曲他滨+替诺福韦富马酸酯组、脂肪食物+替诺福韦富马酸酯组的t1/2降低,cmax、AUC0～72、AUC0～∞、tmax均明显增加。结论:中国西部人群单独给予替诺福韦富马酸酯的药动学特征与国外人群相似,高脂肪饮食以及合用恩曲他滨可改变替诺福韦的药动学特征。OBJECTIVE： To study the pharmacokinetics of Tenofovir disoproxil fumarate （TDF） tablets in healthy volunteers from western China. METHODS： 24 healthy volunteers were randomly divided to 3 groups with 8 in each group. 3 groups were given 300 mg TDF tablets, 300 mg TDF tablets with 200 mg Emtricitabine tablets, 300 mg TDF tablets with high fat diet （the proportion of dietary fat was 50%）, respectively. 2 mL of venous blood was collected at 0, 0.5, 0.75, 1, 1.5, 2, 3, 4,6,8,12,24,36,48,72 h after administration, respectively. The plasma was separated to determine the concentration of tenofovir by HPLC-UV after solid phase extraction, and the pharmacokinetics parameter of tenofovir was calculated by DAS（Ver2.1.1）software. RESULTS： The main pharmacokinetic parameters of tenofovir in 3 groups were as follows：t1/2（18.78±3.28）h, （12.72±2.83）h, （13.08±1.47）h; tmax（1.05±0.16）h,（1.28±0.30）h, （1.55±0.37）h; cmax（290.71±63.21）ng·mL-1, （420.84±96.71） ng·mL-1, （429.06±174.81）ng·mL-1; AUC0～72（1 871.60±377.00）μg·h·L-1, （3 869.42±962.85）μg·h·L-1, （3 569.47±633.47）μg·h·L-1; AUC0～∞（2 284.16±373.54）μg·h·L-1,（4 107.09±974.82）μg·h·L-1, （3 856.00±618.39）μg·h·L-1; CL/F（2.25±0.39）L·h-1·kg-1,（1.28±0.28）L·h-1·kg-1, （1.33±0.20）L·h-1·kg-1. Compared with that of TDF treated group, cmax, tmax,AUC0～72 and AUC0～∞ in TDF＋ emtricitabine treated group and TDF＋high fat diet treated group were increased, and t1/2 were decreased. CONCLUSION： Pharmacokinetic characteristics of tenofovir disoproxil fumarate in Chinese healthy people are similar to that of the foreign crowd. High fat diet and combination with emtricitabine can change the pharmacokinetic properties of tenofovir.

关 键 词：中国西部健康人群 替诺福韦富马酸酯 恩曲他滨 脂肪食物 药动学 高效液相色谱-紫外法 

分 类 号：R969.1[医药卫生—药理学] R978.7[医药卫生—药学]