不同剂量染料木黄酮及其代谢产物在大鼠胆汁中的排泄动力学  

Biliary excretion of genistein and its metabolite at different doses in rats

作　　者：周四元[1] 刘新友[1] 滕增辉[1] 甘洪全[1] 王汝涛[1] 杨志福[1] 梅其炳[1] 

机构地区：[1]第四军医大学药理学教研室,陕西西安710032

出　　处：《药学学报》2006年第8期752-755,共4页Acta Pharmaceutica Sinica

摘　　要：目的研究不同剂量染料木黄酮及其葡糖醛酸化代谢产物在大鼠胆汁内的排泄动力学。方法将染料木黄酮制成混悬液,分别按6.25,12.5和50 mg.kg-1给大鼠灌胃,于灌胃后不同时间收集胆汁,用葡糖醛酸酶溶液处理胆汁。采用高效液相色谱法测定胆汁中染料木黄酮及其葡糖醛酸化代谢产物的浓度。结果3种剂量6.25,12.5和50 mg.kg-1分别给药后,累积以原形从胆汁排泄的药物分别为(42.56±6.54),(75.17±18.87)和(126.60±34.78)μg,累积经胆汁排泄的总药物(原形药物+葡糖醛酸化药物)分别为(108.46±35.23),(423.46±158.31)和(853.74±320.84)μg,葡糖醛酸化代谢产物分别占胆汁排泄总量(原形药物+葡糖醛酸化药物)的60.76%,82.25%和85.17%。结论染料木黄酮在大鼠胆汁中主要以葡糖醛酸结合形式排泄,原形药物及其葡糖醛酸化代谢产物在大鼠胆汁中的排泄呈现明显的非线性剂量依赖性特征。Aim To study the biliary excretion of genistein and its metabolite at different doses in rats. Methods Suspended in 0.5% CMC-Na solution, genistein was orally administered to rats at the dose of 6.25, 12.5 and 50 mg·kg^-1, separately. At various time intervals, the bile was collected. The bile was treated with β-glucuronidase. The genistein in bile was extracted twice by vortexing with 2.0 mL mixture of methyl tert-tubtyl ether and pentane （8： 2）. The organic phase was removed into the tubes and then evaporated in ventilation cabinet. The residue was dissolved in 50 μL of methanol. Twenty μL solution was drawn and detected by high-performance liquid chromatography. Results The accumulative biliary excretion ofgenistein was （42.56±6.54）, （75. 17± 18.87） and （126.60±34.78）μg at the dose of 6. 25, 12.5 and 50 mg·kg^-1, respectively. The total drug （genistein plus glucuronidated genistein） excreted from bile was （ 108.46±35.23）, （423.46±158.31 ） and （853.74±320. 84） μg, and the ratio of glucuronidated genistein was 60.76% , 82.25% and 85. 17% at the dose of 6.25, 12.5 and 50 mgμ·kg^-1, respectively. Conclusion The genistein was excreted mainly in the form of glucuronidated genistein in rat bile. The genistein and glucuronidated genistein were excreted in a nonlinear dose-dependent manner.

关 键 词：染料木黄酮 胆汁排泄 代谢产物 

分 类 号：R969.1[医药卫生—药理学]