大鼠离体肝灌流中葛根素的代谢动力学研究

Metabolizing kinetics of puerarin in the isolated perfused rat liver model

目的:采用大鼠离体肝灌流模型,研究葛根素在大鼠肝脏中的代谢以及维拉帕米、红霉素和利福平对葛根素代谢的影响。方法:以1、10和50mg/L的葛根素溶液对大鼠离体肝脏进行灌流,HPLC法测定灌流液中葛根素的浓度;再分别在含10mg/L的葛根素溶液中加入不同量的维拉帕米、红霉素、利福平后对肝脏进行灌流,测定葛根素的消除情况。结果:1、10和50mg/L的葛根素溶液在肝脏的消除率分别为0.511±0.045、0.378±0.026、0.425±0.040ml/min,且灌流液中葛根素-时间曲线下面积(AUC)与加入剂量呈强正线性相关关系;随灌流液中维拉帕米和红霉素浓度的增大,肝脏对葛根素清除率逐渐降低;随着利福平剂量的增大肝脏对葛根素清除率逐渐增大。结论:葛根素从大鼠肝脏的消除为线性动力学过程;维拉帕米和红霉素对葛根素在大鼠离体肝脏的消除有抑制作用;利福平对葛根素在大鼠离体肝脏的消除有促进作用。

Objective：To investigate the metabolizing kinetics of puerarin and the effect of verapamil, erythremycin and rifampicin on puerarin metabolism by using the isolated perfused rat liver model. Methods： The perfusion experiments took place with the adding of 1, 10 and 50 mg/ L puerarin solution, and the perfused samples were assayed by HPLC for puerarin. Verapamil, erythremycin and rifampicin were added into 10 mg/L puerarin solution, respectively, then perfused to determine the metabolism of puerarin in liver. Results ：The hepatic clearance of 1, 10 and 50 mg/L puerarin were 0.511 ±0.045,0.378 ±0. 026 and 0. 425 ±0. 040 ml/min, respectively. The areas under the concentration time curves （AUC） and doses of perfused solution exhibited linear relationship. With the increase of the concentration of verapamil and erythromycin, the hepatic clearance of puerarin was decreased, and with the increase of the concentration of rifampicin, the hepatic clearance of puerarin was increased. Condusion： The elimination of puerarin exhibited linear pharmacokinetics in isolated liver. The elimination of puerarin was inhibited when verapamil and erythromycin were co-perfused, and rifampicin accelerated the elimination of puerarin.