富马酸替诺福韦二吡呋酯胶囊在中国人体内的药代动力学  

Pharmacokinetics of tenofovir disoproxil fumarate capsule in Chinese volunteers

作　　者：姜莉苑[1] 丁黎[1] 钟水生[1] 刘冰[1] 陈迪[1] 文爱东[2] 

机构地区：[1]中国药科大学药物分析教研室,南京210009 [2]第四军医大学西京医院药剂科,西安710032

出　　处：《中国药科大学学报》2013年第4期348-351,共4页Journal of China Pharmaceutical University

摘　　要：研究富马酸替诺福韦二吡呋酯胶囊在中国人体内的药代动力学特征。12名健康受试者依次进行低剂量(300mg)单、多次给药;高(600 mg)剂量单次给药和低剂量饮食影响单次给药的药代动力学试验,计算药代动力学参数。受试者单次口服300 mg和600 mg受试制剂后,替诺福韦的cmax分别为(305.4±96.4)和(590.0±149.6)ng/mL,AUC0-72 h分别为(2 396±489)和(4 465±1 042)ng.h/mL,t1/2分别为(19.9±2.4)和(21.9±3.0)h。结果显示替诺福韦在300～600 mg剂量范围内呈现线性药代动力学特征,体内过程不受性别差异的影响。与空腹给药相比,高脂餐后给药的tmax延后1.6 h,AUC0-72 h提高约32%。多次给药达稳态后,替诺福韦的稳态血药浓度波动度为2.7±0.6,累积常数Rcmax为1.3±0.3,RAUC为1.7±0.4,在人体内的暴露量增加约70%。To investigate the pharmacokinetics of tenofovir disoproxil fumarate（TDF） capsule in Chinese volunteers.A phase I,3-period study was performed in healthy Chinese subjects.12 Healthy subjects received either single 300 mg,multiple 300 mg and single 600 mg doses of TDF under fasted conditions,or received single 300 mg doses under fed condition.For 300 mg and 600 mg single administration of TDF,the cmax data were（305.4±96.4） and（590.0±149.6） ng/mL,respectively,and the AUC0-72 h data were（2 396±489） and（4 465±1 042） ng ·h/mL,respectively.In the dose range of 300-600 mg,tenofovir demonstrated linear pharmacokinetic characteristics in Chinese volunteers.No significant gender difference in the pharmacokinetic parameters was found.High fat food decreased the absorption rate of tenofovir,but increased its exposure.In the multiple-dose study at 300 mg dose for 7 consecutive days,the degree of fluctuation（DF） was 2.7±0.6,and the accumulation parameter（Rcmax） and（RAUC） were 1.3±0.3 and 1.7±0.4,respectively.Compared with the single dose administration,an increased exposure of 70% in AUC0-τ of tenofovir was observed after a multiple administration.

关 键 词：替诺福韦 胶囊 LC-MS MS 药代动力学 

分 类 号：R969.1[医药卫生—药理学]