论文部分内容阅读
目的研究健康受试者口服盐酸度洛西汀肠溶片后的体内药物代谢动力学特征。方法 20名健康受试者,男女各半,单次和多次口服盐酸度洛西汀肠溶片,进行药动学实验;采用LC-MS/MS法测定血浆中盐酸度洛西汀浓度,DAS 2.0进行药动学模型拟合和参数计算,SPSS 17.0软件进行统计分析。结果盐酸度洛西汀肠溶片的体内药动学符合一室开放模型,低、中、高剂量单次给药的主要药动学参数:实测值计算的平均Cmax分别为13.85±7.37、29.86±13.87、44.47±21.80μg·L-1,Tmax分别为7.60±3.47、6.80±1.40、6.80±1.40 h,统计矩计算的平均t1/2分别为13.93±6.88、11.57±2.34、12.19±1.73 h,AUC0-t分别为268.15±204.6、531.02±385.13、843.53±634.50μg·L-1·h-1;连续给药的主要药动学参数Cmax、Cmin、Cav分别为47.37±23.59、19.47±10.55、33.09±17.11μg·L-1,Tmax、t1/2分别为6.57±1.59、13.90±2.80 h,AUC0-t为1.13±0.68 mg·L-1·h-1。结论 20～60 mg盐酸度洛西汀肠溶片呈线性动力学特点,主要药物代谢动力学参数无性别差异,多次给药后体内无明显蓄积作用。
Objective To study the in vivo pharmacokinetics of oral duloxetine hydrochloride enteric-coated tablets in healthy subjects. Methods Twenty healthy subjects, half male and half female, were dosed orally with duloxetine hydrochloride enteric-coated tablets one after the other for pharmacokinetic study. The concentration of duloxetine hydrochloride in plasma was determined by LC-MS / MS, DAS 2.0 pharmacokinetic model fitting and parameter calculation, SPSS 17.0 software for statistical analysis. Results The pharmacokinetics of duloxetine hydrochloride enteric-coated tablets conformed to the one-compartment open model. The main pharmacokinetic parameters of low, medium and high dose single-dose administration were as follows: The calculated average Cmax values were 13.85 ± 7.37,29.86 ± 13.87,44.47 ± 21.80μg · L-1, Tmax were 7.60 ± 3.47,6.80 ± 1.40,6.80 ± 1.40 h, respectively, and the average t1 / 2 of statistical moments were 13.93 ± 6.88, 11.57 ± 2.34 and 12.19 ± 1.73 h , AUC0-t were 268.15 ± 204.6,531.02 ± 385.13,843.53 ± 634.50μg · L-1 · h-1 respectively. The main pharmacokinetic parameters Cmax, Cmin and Cav for continuous administration were 47.37 ± 23.59 and 19.47 ± 10.55 , 33.09 ± 17.11μg · L-1, Tmax and t1 / 2 were 6.57 ± 1.59 and 13.90 ± 2.80 h, respectively. The AUC0-t was 1.13 ± 0.68 mg · L-1 · h-1. Conclusions 20 ~ 60 mg duloxetine hydrochloride enteric-coated tablets showed a linear kinetic characteristic. The main pharmacokinetic parameters were non-sex difference. There was no significant accumulation in vivo after multiple administrations.