Pharmacokinetics and modeling of quercetin and metabolites
Pharmacokinetics and modeling of quercetin and metabolites
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DOI：
10.1007/s11095-005-4584-1
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发表时间：
2005-06-01
影响因子：
3.7
通讯作者：
Chow, MSS
中科院分区：
文献类型：
--
作者：
Chen, X;Yin, OQP;Chow, MSS
目的。测定槲皮素及其葡萄糖醛酸苷/硫酸盐结合物在大鼠体内的药代动力学，建立同时描述其静脉和口服给药的药代动力学模型。在口服、门脉内和静脉给药后，用高效液相色谱法测定了一系列的血浆、尿液和粪便中的浓度。在连锁大鼠模型上以及口服含有槲皮素及其代谢物的胆汁后，对肠-肝再循环进行了评估。根据实验数据，建立并验证了一个特定的房室模型来描述和预测口服和静脉给药后的药物浓度-时间分布。虽然总吸收量高达59.1%，但只有5.3%的未改变的槲皮素具有生物利用度。口服后，93.3%的槲皮素在肠道中代谢，只有3.1%在肝脏中代谢。没有观察到明显的肠-肝再循环，槲皮素及其结合代谢物。药代动力学模型与槲皮素及其结合物的观察数据吻合较好。我们的研究阐明了肠道、肝脏和胆汁在Qercetin及其结合物的代谢和排泄中的相对重要性。药代动力学模型似乎适合于描述槲皮素及其结合物的吸收和处置，并可适用于其他经历类似药代动力学途径的黄酮类化合物。
Purpose. To determine the pharmacokinetics of quercetin and its glucuronide/sulfate conjugates and to develop a pharmacokinetic model to simultaneously describe their disposition after intravenous and oral administration in rats.Methods. After oral, intraportal, and intravenous administration of quercetin, serial plasma, urine, and fecal concentrations of quercetin and its conjugates were determined by an HPLC method. Enterohepatic recirculation was evaluated in a linked-rat model as well as after oral administration of bile containing quercetin and its metabolites. Based on the experimental data, a specific compartmental model was developed and validated to describe and predict the plasma concentration-time profiles of quercetin and its conjugates after oral and intravenous administration.Results. Only 5.3% of unchanged quercetin was bioavailable, although the total quercetin absorbed was as high as 59.1%. After oral administration, about 93.3% of quercetin was metabolized in the gut, with only 3.1% metabolized in the liver. No significant enterohepatic recirculation was observed for both quercetin and its conjugated metabolites. The pharmacokinetic model fitted well the observed data of quercetin and its conjugates.Conclusions. Our study clarifies the relative importance of the gut, liver, and bile in the metabolism and excretion of quercetin and its conjugates. The pharmacokinetic model appears to be suitable for describing the absorption and disposition of the quercetin and its conjugates and may be applicable to other flavonoids that undergo similar pharmacokinetic pathways.