在大鼠体内非瑟酮的药代动力学和胆汁排泄。

Pharmacokinetics and Biliary Excretion of Fisetin in Rats.

机构信息

Institute of Traditional Medicine, School of Medicine , National Yang-Ming University , 155 Li-Nong Street, Section 2 , Taipei 112 , Taiwan.

Department of Urology, School of Medicine , National Yang-Ming University , Taipei 112 , Taiwan.

出版信息

J Agric Food Chem. 2018 Jun 27;66(25):6300-6307. doi: 10.1021/acs.jafc.8b00917. Epub 2018 Jun 14.

DOI:10.1021/acs.jafc.8b00917

PMID:29862816

Abstract

The hypothesis of this study is that fisetin and phase II conjugated forms of fisetin may partly undergo biliary excretion. To investigate this hypothesis, male Sprague-Dawley rats were used for the experiment, and their bile ducts were cannulated with polyethylene tubes for bile sampling. The pharmacokinetic results demonstrated that the average area-under-the-curve (AUC) ratios ( k (%) = AUC/AUC) of fisetin, its glucuronides, and its sulfates were 1:6:21 in plasma and 1:4:75 in bile, respectively. Particularly, the sulfated metabolites were the main forms that underwent biliary excretion. The biliary excretion rate ( k (%) = AUC/AUC) indicates the amount of fisetin eliminated by biliary excretion. The biliary excretion rates of fisetin, its glucuronide conjugates, and its sulfate conjugates were approximately 144, 109, and 823%, respectively, after fisetin administration (30 mg/kg, iv). Furthermore, biliary excretion of fisetin is mediated by P-glycoprotein.

摘要

本研究的假设是，漆黄素及其相 II 结合型可能部分经胆汁排泄。为了验证这一假设，本实验使用雄性 Sprague-Dawley 大鼠，用聚乙烯管对其胆管进行插管以采集胆汁样本。药代动力学结果表明，在血浆中，漆黄素、其葡萄糖醛酸苷和硫酸酯的平均曲线下面积（AUC）比值（k（%）= AUC/AUC）分别为 1:6:21，在胆汁中分别为 1:4:75。特别是，硫酸酯代谢物是主要的经胆汁排泄的形式。胆汁排泄率（k（%）= AUC/AUC）表示经胆汁排泄消除的漆黄素的量。在给予漆黄素（30mg/kg，iv）后，漆黄素、其葡萄糖醛酸苷轭合物和硫酸酯轭合物的胆汁排泄率分别约为 144%、109%和 823%。此外，漆黄素的胆汁排泄是由 P-糖蛋白介导的。