單劑量與多劑量柚皮啟及柚皮啟元於大白鼠之藥物動力學   全文下載

Pharmacokinetics and Conjugation Metabolism of Naringin and Naringenin in Rats after Single Dose and Multiple Dose Administrations

柚皮?（Naringin）及柚皮?元（naringenin）為柑橘屬植物中之主要黃酮類化合物。本研究以大白鼠探討柚皮?及柚皮?元單劑量與多劑量之動力學。柚皮?元分別以單劑量靜脈注射與口服，而柚皮?則分別以單劑量與多劑量（每天二次共九天）口服投予大白鼠。血清撿品以sulfatase及β-glucuronidase分別水解前、後，以高效液相層析法定量柚皮?元之濃度。柚皮?元靜脈注射後，快速形成硫酸及葡萄糖醛酸結合態代謝物，其原形分子快速減少；而口服給予柚皮?元及柚皮?時，則幾無原形分子，只有結合態代謝物存在血循環中。柚皮?多劑量投予後，第五天可達穩定狀態。口服投予柚皮?與柚皮?元後，柚皮?元之硫酸結合代謝物之血中濃度皆遠高於葡萄糖醛酸結合態代謝物。總之，柚皮?及柚皮?元於大白鼠口服給藥後，血循環中皆以柚皮?元之結合態代謝物存在。因此，有關柚皮?及柚皮?元之生物活性研究應著重其結合態代謝物，特別是硫酸結合代謝物。

Naringin and naringenin are major flavonoids in citrus fruits. This study investigated the pharmacokinetics of naringin and naringenin in rats. Single dose of naringenin was administered to rats via intravenous bolus and oral route, whereas naringin was given orally as single dose and multiple doses (twice daily for 9 days). The serum concentrations of naringenin were assayed by HPLC method prior to and after hydrolysis with β-glucuronidase and sulfatase, respectively. After intravenous bolus of naringenin, naringenin sulfates and glucuronides emerged instantaneously, the profile of naringenin parent form declined rapidly. In contrast, when naringenin and naringin was orally administered, naringenin sulfates and glucuronides were found almost exclusively circulating in the bloodstream, whereas no naringin and naringenin was detected in most serum samples. After multipledose administration of naringin, naringenin sulfates and glucuronides gradually accumulated in the circulation and reached steady state on day 5. The profile of naringenin sulfates was much higher than that of naringenin glucuronides. In conclusion, the sulfates and glucuronides of naringenin were exclusively present in the circulation whether naringenin or naringin was orally given to rats. Therefore, pharmacologists should focus more on the bioactivities of conjugated metabolites of naringenin, in particular naringenin sulfates.