中国健康志愿者单次和多次口服阿德福韦酯片的药动学

Pharmacokinetics of Adefovir Dipivoxil Tablets in Chinese Healthy Subjects

目的研究健康受试者单次和多次口服阿德福韦酯片后的药动学过程。方法 12名中国男性健康受试者单次po和多次po 10 mg阿德福韦酯片;采用液相色谱-串联质谱联用法(LC-MS/MS)测定阿德福韦酯活性代谢物阿德福韦的血药浓度。用DAS2.0程序计算主要药动学参数,并进行统计分析。结果健康志愿者单次和多次口服阿德福韦酯片10 mg后,阿德福韦的ρmax分别为(24±9)和(24±8)μg.L-1,tmax分别为(1.3±0.7)和(1.5±0.6)h,t1/2分别为(7.4±1.2)和(8.5±2.1)h,AUC0-24h分别为(210±54)和(213±73)μg.h.L-1,AUC0-∞分别为(236±64)和(250±90)μg.h.L-1。多次po阿德福韦酯片后ρsasv为(8.90±3.06)μg.L-1,DF为(2.52±0.66)。结论阿德福韦酯片单次与多次口服的主要药动学参数无显著性差异,体内药物无蓄积现象,耐受性良好。

OBJECTIVE To investigate the pharmacokinetics of 10 mg adefovir dipivoxil tablet formulations in 12 Chinese healthy subjects after a single dose and multiple doses. METHODS A single dose and multiple doses of the formulations of adefovir dipivoxil tablets were given to each of 12 healthy male subjects. The concentrations of adefovir in plasma were determined by LC-MS/ MS. The pharmacokinetic parameters were calculated by DAS2. 0 programme. RESULTS The obtained pharmacokiuetic parameters of adefovir following adefovir dipivoxil tablets in a single dose and multiple doses group were as follows ： Pmax were （ 24 ± 9 ）, （ 24 ± 8 ） μg·L-1 ;AUC0_24h were （210 ±54 ）, （213 ±73） ;AUCμg·h·L-1 were（236 ±64）, （250 ±90） μg·h·L-1;t1/2 were （7.4 ± 1.2）, （ 8.5 ± 2. 1 ） h ; tmax were （ 1.3 ± 0. 7 ） , （ 1.5 ± 0. 6 ） h , respectively. Other main parameters in multiple doses group were pav （ 8.90 ± 3.06） and DF （2. 52 ±0. 66 ）. CONCLUSION There was no significant difference in pharmacokinetic parameters between single dose and multi-dose group. There is no accumulation following muhiple doses of adefovir dipivoxil. Adefovir dipivoxil tablets were safe and well tolerated in Chinese subjects.