非布司他片在健康人体内的药动学研究

目的: 建立血浆中非布司他的HPLC-MS/MS定量分析方法,对非布司他片的人体药动学进行研究,为该药临床合理使用提供参考. 方法: 对12名中国健康志愿者(男、女各半)依次进行40 mg与80 mg 2个剂量单次口服给药,以及80 mg剂量每天1次连续7 d的多次口服给药.采用HPLC-MS/MS法测定血药浓度,WinNonLin 6.3软件计算药动学参数,IBM SPSS Statistics 19软件对结果进行统计分析. 结果: 单次口服非布司他片40、80 mg和多次口服80 mg后,血浆中非布司他的AUC_0→t分别为(7 320±2 198)、(15 121±4 328)、(14 376±4 089)ng·h·mL^-1,C_max分别为(2 078±533.2)、(4 094±1 282)、(3 841±1 071)ng·mL^-1,T_max分别为(1.69±0.91)、(1.54±0.74)、(1.58±1.06)h,t_1/2分别为(6.09±1.72)、(7.07±2.37)、(6.19±1.94)h. 结论: 单剂量口服给药试验表明,在40到80 mg剂量范围内,口服非布司他在健康中国人体内的药动学过程呈现剂量依赖性;多剂量口服给药试验表明,非布司他在健康中国人体内几乎无蓄积现象;非布司他在不同性别中国人群体内的药动学过程无明显差异.

Objective: To establish an HPLC-MS/MS quantitative analysis method for febuxostat in plasma,so as to study the pharmacokinetics of febuxostat tablets in healthy Chinese volunteers,and provide references for rational clinic use of febuxostat. Methods: Twelve healthy volunteers(with even gender ratio in each group)were recruited for the study and received single doses of 40 mg or 80 mg febuxostat tablets or multiple doses of 80 mg febuxostat tablets. The plasma concentration of febuxostat was measured by an HPLC-MS/MS method. The pharmacokinetics parameters were calculated using software WinNonLin(version 6.3). The statistical analysis was performed using IBM SPSS Statistics 19. Results: Following oral administration of febuxostat tablets,the main pharmacokinetics pa rameters were calculated as follows:AUC_0→twere(7 320±2 198),(15 121±4 328),(14 376 ±4 089)ng·h·mL^-1;C_max were(2 078±533.2),(4 094±1 282),(3 841±1 071)ng·mL^-1;T_max were(1.69±0.91),(1.54±0.74),(1.58±1.06)h;t_1/2 were(6.09±1.72),(7.07±2.37),(6.19±1.94)h for single doses of 40 mg,80 mg and multiple doses of 80 mg febuxostat,respectively. Conclusion: The single dose experiment indicated that the febuxostat followed a dose dependent manner in healthy Chinese volunteers at the investigated dose ranged from 40 to 80 mg. No significant difference of drug accumulation of multiple doses was observed in this study. In addition,there was no significant difference of pharmacokinetics between males and females in Chinese population.