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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。
OBJECTIVE To determine the concentration of fenofibric acid, the active metabolite of fenofibrate, in rat plasma by RP-HPLC and to study the pharmacokinetics of fenofibrate in rats after a single oral dose of fenofibrate. Methods Eighteen Sprague-Dawley rats were randomly divided into three groups. After oral administration of fenofibrate suspension at low, medium and high doses (10, 50 and 100 mg · kg -1), respectively, The concentration of drug in plasma was determined by HPLC, and the plasma concentration-time curve was drawn. The pharmacokinetic parameters were fitted by DAS 2.1.1 software. Results The drug-time curves of fenofibric acid in high, medium and low doses were in accordance with the two-compartment model of oral absorption. The main pharmacokinetic parameters were Cmax 18.15 ± 3.02,8.68 ± 1.69,1.68 ± 0.42μg · mL- 1; Tmax 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 Lh-1; AUC0-t was 209.07 ± 36.25, 92.20 ± 23.47 and 20.17 ± 6.54μg · mL-1 · h-1, respectively; AUC0-∞ was 210.22 ± 36.29, 93.87 ± 23.51 and 21.27 ± 6.53μg · mL-1 · h-1. Conclusion The RP-HPLC method can accurately determine the concentration of fenofibrate in plasma and meet the requirements of pharmacokinetic studies. Pharmacokinetics of fenofibrate in rats was linear pharmacokinetic in the dose range.