【摘要】 目的研究阿德福韦酯(抗病毒药)连续口服后在中国健康人体的药代动力学和安全性。方法采用随机、双盲、安慰剂对照设计,15名健康志愿者第1天单剂口服阿德福韦酯10mg;第3天起,每日口服阿德福韦酯10mg1次,连用5天,用液相色谱-串联质谱法测定血浆和尿液中的药物浓度,计算药代动力学参数。结果单次和多次口服阿德福韦酯10mg达稳态后,主要药代动力学参数:AUC0-t分别为(205.8±53.1)、(288.8±90.6)ng.h.mL-1;Cmax分别为(21.5±5.1)、(26.7±7.2)ng.mL-1;tmax分别为(1.06±0.41)、(0.94±0.44)h;t1/2分别为(8.12±2.02)、(9.68±2.84)h。单次口服阿德福韦酯48h内,以原形排入尿中的占给药剂量的(67.8±15.7)%。结论阿德福韦酯主要经肾脏排泄,连续给药未见蓄积,血药浓度服药后在第4天达稳态,较安全。更多还原

【Abstract】 Objective To study the pharmacokinetics and safety of multiple oral administration of adefovir dipivoxil(ADV) tablets in Chinese healthy volunteers. Methods This was a single center,investigator and subject-blind,randomized ,placebo controlled study. Fifteen healthy volunteers (the ratio of ADV and placebo was 4∶1 ) were given 10 mg ADV or placebo once a day for 6 days. The plasma concentrations after first and seventh day and urine concentrations in 48 h after first day were determined by HPLC/MS/MS.Results The main pharmacokinetic parameters of ADV after oral a single dose (10 mg) and multiple-dose were as follow: AUC0-t were (205.8±53.1),(288.8±90.6)ng.h.mL-1;Cmax were (21.5±5.1),(26.7±7.2) ng.mL-1;tmax were (1.06±0.41),(0.94±0.44)h;t1/2 were (8.12±2.02),(9.68±2.84)h,respectively. In 48 h following a single dose of 10 mg ADV,the dose elimininated by kidney was (67.8±15.7)%.Conclusion ADV eliminates mainly by kidney. There is not cumulation of ADV in plasma after multiple-dose of 10 mg. The plasma concentrations reach stabilization at 4th days after oral administration. ADV multiple-dose of 10 mg were safe in Chinese healthy subjects.更多还原