芸香與槲皮素於鼠體內之生可用率及代謝動力學   全文下載

Bioavailability and Metabolic Pharmacokinetics of Rutin and Quercetin in Rats

芸香啟與槲皮素為黃酮配醣體及非醣體，大量存在於中草藥及植物性食品中。本研究主要比較兩者於大白鼠體內之代謝動力學。大白鼠以靜脈注射（33 μmol/kg）、口服（165 μmol/kg）投予槲皮素，芸香啟則以口服（328μmol/kg）投予。於特定時間點心臟採血，血清檢品分別經葡萄糖醛酸與硫酸?水解前後，利用HPLC方法定量槲皮素。數據處理則利用WINNONLIN軟體中非室模式分析其藥物動力學參數。結果顯示，靜脈注射槲皮素後，93.8%以槲皮素結合態代謝物循環於體內。口服槲皮素後，幾全以槲皮素之硫酸與葡萄糖醛酸代謝物存在於血流中，槲皮素原形則未測得。經劑量校正後，槲皮素於大白鼠之口服生可用率為53%。口服芸香啟時，幾全以槲皮素硫酸與葡萄糖醛酸代謝物循環於體內，並未測得芸香啟及槲皮素。槲皮素口服吸收率明顯高於芸香啟。總之，大白鼠不論口服槲皮素或芸香啟，血清中皆以硫酸槲皮素與葡萄糖醛酸槲皮素為主要代謝物存在。

Rutin and quercetin, a flavone glycoside and its aglycone, are the flavonoids most widely and abundantly present in herbs and plant foods. The aim of this study was to characterize and compare the bioavailability and metabolic pharmacokinetics of rutin and quercetin in rats. Quercetin was administered intravenously (33 μmol/kg) and orally (165 μmol/kg), while rutin was administered only orally (328 μmol/kg) to rats. Blood samples were withdrawn via cardiopuncture at specific time points. An HPLC method was used to determine the concentrations of quercetin before and after hydrolysis using β-glucuronidase and sulfatase, respectively. The pharmacokinetic parameters were calculated using noncompartment model of WINNONLIN. The results showed that after intravenous administration of quercetin, 93.8% of the dose was circulating as its sulfates and glucuronides. After oral administration of quercetin, the glucuronides and sulfates of quercetin were exclusively present in the bloodstream, whereas the parent form of quercetin was not detected. The oral absorption rate of quercetin was 53% compared to intravenous administration after dose correction. When rutin was orally administered, sulfates and glucuronides of quercetin were exclusively present in the bloodstream, whereas rutin and quercetin were not detected. Quercetin showed higher oral absorption rate than rutin. In conclusion, quercetin sulfates and quercetin glucuronides represent the major metabolites either rutin or quercetin was administered to rats.