淫羊藿苷在大鼠体内的药代动力学

Pharmacokinetics of icariin in rats

目的：研究淫羊藿制剂中淫羊藿苷（Ｉｃａ）在大鼠体内的吸收、分布、排泄、生物利用度及蛋白结合率等药动学特性。方法：淫羊藿苷在生物样品的浓度用高效液相色谱法测定。结果：淫羊藿注射液含Ｉｃａ１０，１５和２２ｍｇｋｇ－１ｉｖ给药，其药时过程符合二室开放模型特征，ｔ１／２β分别为（１７０±７５．１）、（１６８±４１．７）和（２０９±４０．１）ｍｉｎ。按含Ｉｃａ１０，１５ｍｇｋｇ－１ｉｖ后，其药时过程符合线性动力学，按含Ｉｃａ２２ｍｇ·ｋｇ－１ｉｖ后为非线性动力学。大鼠灌胃及肝门静脉给药后，其药时过程符合单室开放一级吸收模型特征。体内绝对生物利用度为１２．０％，肝门静脉注射的绝对生物利用度为４５．１７％。按含Ｉｃａ２２ｍｇｋｇ－１ｉｖ后，结果表明服药２ｈ后药物可广泛分布于各组织中，主要集中在肺、血浆中，心、肝、肾次之，脾和脑较少。尿、胆汁和粪的排泄实验表明：尿、胆汁和粪２４ｈ排泄量分别占给药量的１．９９％，０．０６６％和１２．８３％。Ｉｃａ的血浆蛋白结合率为８０．０５％。

OBJECTIVE:To study the absorption,distribution,excretion,bioavailability and protein binding of icariin in Epimedium preparation in rats.METHODS:A HPLC asssy was used to determine the icariin concentrations in biological samples.RESULTS:The concentration time profiles of icariin in rats after iv of 10,15and 22mg/kg were shown to fit a two compartment open model with half lives of 170±75.1,168±41.7and 209±40.1 min,respectively.At the iv doses of 10 and 15 mg/kg,the elimination of icariin from plasma was found to be in accord with linear kinetics,but when the dosage was 22mg/kg,a non linear kinetics was observed.The concentration time curves of icariin in rats fited one compartment open model with first order absorption after oral administration and hepatic portal vein injection, respectively.The absolute availability was 12.02%,the first pass effect of liver was 45.17% .Two hours after oral administration of icaiin to normal rats,the highest level of icariin was found in the lung and plasma,while appreciable icariin was found in the heart,liver and kidney.The level of icariin in spleen and brain was very lower,the excreted amount from urine,faeces and bile was very small,and the accumulated amount for 24h was only 1.99%,12.83% and 0.066% of the administration dosage,respectively.Plasma protein binding was about 80.05%.CONCLUSION:This study will provide a scientific basis for the quality evaluation and dosage formsrefo modification of icariin.