HPLC测定大鼠血浆中非诺贝特的活性代谢物及其药动学研究

目的采用RP-HPLC测定大鼠血浆中非诺贝特活性代谢物非诺贝特酸的浓度,并研究单次口服不同剂量非诺贝特在大鼠体内的药动学。方法将18只SD大鼠随机分为3组,分别按体重口服低、中、高剂量(10、50、100 mg·kg-1)非诺贝特混悬液后,采用经过验证的RP-HPLC法测定血浆中药物的浓度,绘制血药浓度-时间曲线,以DAS 2.1.1软件拟合药动学参数。结果高、中、低剂量非诺贝特酸的药-时曲线均符合口服吸收的二室模型,主要药动学参数:Cmax分别为18.15±3.02、8.68±1.69、1.68±0.42μg·mL-1;Tmax分别为6.80±0.75、6.33±1.75、6.50±1.38 h;t1/2分别为4.44±1.03、5.38±1.91、4.76±1.12 h;Cl/F分别为0.49±0.08、0.56±0.13、0.50±0.11 L.h-1;AUC0-t分别为209.07±36.25、92.20±23.47、20.17±6.54μg·mL-1·h-1;AUC0-∞分别为210.22±36.29、93.87±23.51、21.27±6.53μg·mL-1·h-1。结论所用RP-HPLC法能够准确地测定非诺贝特酸的血药浓度,满足药动学研究的要求。在给药剂量范围内,非诺贝特酸在大鼠体内的药动学符合线性药动学规律。

Determination of Fenofibrate metabolite in the rat plasma by HPLC and pharmacokinetic study

OBJECTIVE To develop a reversed-phase HPLC method for determining the plasma drug concentration of fenofibric acid in rats and apply it to a pharmacokinetic study in rats at different doses of Fenofibrate by gavage.METHODS Eighteen SD rats were randomly divided into three groups and given single oral doses of Fenofibrate at 10,50,100 mg·kg^-1 as the low,middle and high dose respectively.Then multiple blood samples were collected and the concentrations of fenofibric acid in plasma were determined by the validated RP-HPLC method.The plasma concentration-time curves were constructed and the pharmacokinetic parameters were calculated by the DAS 2.1.1 software.RESULTS The pharmacokinetics of fenofibric acid was best fitted to the two-compartment model in rats at doses of 10,50 and 100 mg·kg^-1.The main pharmacokinetic parameters of fenofibric acid in the three groups rats were as follows:C_max were 18.15±3.02,8.68±1.69,1.68±0.42 μg·mL^-1,T_max were 6.80±0.75,6.33±1.75,6.50±1.38 h,t₁/2 were 4.44±1.03,5.38±1.91,4.76±1.12 h,Cl/F were 0.49±0.08,0.56±0.13,0.50±0.11 L·h^-1 and AUC₀-t were 209.07±36.25,92.20±23.47,20.17±6.54 μg·mL^-1·h^-1,and AUC₀-∞ were 210.22±36.29,93.87±23.51,21.27±6.53 μg·mL^-1·h^-1.CONCLUSION An RP-HPLC method for the determination of rats plasma fenofibric acid concentration was developed and successfully applied to a pharmacokinetic study.The fenofibric acid in the three groups displayed a linear pharmacokinetics in the dose range of 10 to 100 mg·kg^-1.