盐酸度洛西汀肠溶片在健康人体内的药物代谢动力学研究

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。

Pharmacokinetics of Duloxetine hydrochloride enteric tablet after oral administration in healthy volunteers

OBJECTIVE To study the pharmacokinetics of Duloxetine hydrochloride enteric-coated tablet in healthy volunteers.METHODS Twenty healthy volunteers were enrolled to receive single doses and multiple-dose of Duloxetine hydrochloride enteric tablet in an open randomized study.The plasma concentrations of DLX were determined by HPLC-MS/MS.The DAS 2.0 was used to fit the concentration-time data and to calculate the pharmacokinetic parameters.SPSS 17.0 program was used for statistical analysis.RESULTS The pharmacokinetic profiles of Duloxetine hydrochloride enteric tablet were described by a one-compartment model.The main pharmaeokinetic parameters of DLX after single dose of low,middle,high were as follows:C_max were 13.85±7.37,29.86±13.87 and 44.47±21.80 μg·L^-1,T_max were 7.60±3.47,6.80±1.40 and 6.80±1.40 h,t₁/2 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 and 843.53±634.50 μg·L^-1·h^-1,respectively.The main pharmacokinetic parameters of DLX after multiple-dose administration were as follows:C_max,C_min,C_av was 47.37±23.59,19.47±10.55,33.09±17.11 μg·L^-1,T_max was 6.57±1.59 h,t₁/2 was 13.90±2.80 h,AUC₀-t was 1.13±0.68 mg·L^-1·h^-1,respectively.CONCLUSION The results showed that Duloxetine hydrochloride performance a linear kinetics in the sigle oral administration between 20-60 mg.The main pharmacokinetic parameters had no significant difference between genders.There was no significant accumulation after multiple dosing.