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    题名: 柳橙汁黃酮之代謝動力學及大黃、黃芩對胺甲葉酸動力學之影響;Metabolic Pharmacokinetics of Flavonoids of Orange Juice and the Effect of Rhei Rhizoma, Scutellariae Radix on Methotrexate Pharmacokinetics
    作者: 陳仁元;Jen-Yuan Chen
    贡献者: 中國醫藥大學藥物化學研究所
    关键词: 黃酮;動力學;大黃;黃芩;胺甲葉酸;Flavonoids;Pharmacokinetics;Rhei Rhizoma;Scutellariae Radix;Methotrexate
    日期: 2004
    上传时间: 2010-01-20 16:55:38 (UTC+8)
    摘要: 橙皮? (hesperidin) 及橙皮?元 (hesperetin) 為天然黃酮類化合物，存在於柑橘屬植物中。文獻報導橙皮?及橙皮?元具有許多優越的藥理活性，如抗發炎、抗過敏及抗氧化等。本研究以大白鼠探討橙皮?及橙皮?元於鼠體內之代謝動力學。血清檢品於以 sulfatase與 b-glucuronidase分別水解前、後，利用高效液相層析法定量原形之橙皮?元與結合態代謝物。橙皮?元靜脈注射給藥後，橙皮?元快速代謝成結合態代謝物，而原形分子只短暫存在於血清中。口服給予橙皮?元，則只有結合態代謝物存在血中。比較口服與靜脈注射之血藥面積顯示，口服橙皮?元之吸收率為45.2 %。橙皮?口服給藥後，橙皮?與橙皮?元之原形分子或結合態代謝物皆未檢出。 柳橙汁富含橙皮?與柚皮芸香?。本研究探討柳橙汁中此兩黃酮類配醣體於健康人體內之尿藥動力學。受試者飲用柳橙汁後，分段收集24小時內之尿液，於以 sulfatase與 b-glucuronidase分別水解前、後，利用高效液相層析法定量橙皮?元、柚皮?元及其結合態代謝物。結果顯示，飲用柳橙汁後，橙皮?、柚皮芸香?及其?元皆無法檢出，而以橙皮?元及柚皮?元之結合態代謝物存在於尿中，排出率分別為飲入劑量之3.9 % 與2.5 %。 胺甲葉酸(Methotrexate，MTX)為抗癌藥物，治療指數狹窄，用藥的安全性值得關注。本研究探討大黃與黃芩水煎劑於大鼠體內對胺甲葉酸動力學之影響。利用螢光偏極免疫分析法定量胺甲葉酸之血中濃度。結果顯示併服大黃及黃芩水煎劑，使口服胺甲葉酸之血藥面積(AUC0-2880) 與平均滯留時間 (MRT) 皆顯著增加，甚至導致死亡；而對靜脈注射胺甲葉酸則無影響。為了用藥安全與療效之考量，服用胺甲葉酸之病患，應避免與大黃或黃芩併服及含其之製劑。; Hesperidin and hesperetin, are naturally occurring flavanoids abundant in Citrus plants. They were reported to possess many beneficial pharmacological activities including anti-inflammation, anti-allergic and anti-oxidation effects. In this study, the pharmacokinetics of hesperidin and hesperetin were investigated in rats. The serum concentrations of hesperetin were assayed by HPLC method prior to and after hydrolysis with sulfatase and b-glucuronidase, respectively. After iv bolus of hesperetin, hesperetin sulfates and glucuronides were found predominately circulating in the bloodstream where the parent form hesperetin was transiently present. When hesperetin was orally administered, hesperetin sulfates and glucuronides were the major metabolites. The comparison of AUCs of hesperetin and its conjugated metabolites between po and iv administrations indicated that the absrption rate of hesperetin was 45.2%. However, neither parent forms of hesperidin and hesperetin nor their sulfates and glucuronides was detected in serum after oral administration of hesperidin. Orange juice is rich in hesperidin and narirutin. In this study, the urine pharmacokinetics of there two flavonoid glycosides in orange juice were investigated in healthy humans. Urine samples were collected from volunteers within 24h after giving orange juice and assayed for hesperetin, naringenin and their conjugate metabolites by HPLC prior to and after hydrolysis with sulfatase and b-glucuronidase, respectively. No hesperidin, narirutin and their aglycones were detected. The cumulated urinary recoveries (% of dose) of conjugate metabolites of hesperetin and naringenin were 3.9 % and 2.5 %, respectively. Methotrexate (MTX) is a potent anticancer agent with narrow therapeutic range and thus more attention is needed to paid to the safety of MTX. This study aimed to investigate the effects of decoctions of Rhei Rhizoma and Scutellariae Radix on MTX pharmacokinetics in rats. Blood samples were assayed for MTX by a specific monoclonal FPIA (Fluorescence Polarization Immunoassay) method. Coadminstrations with decoction of Rhei Rhizoma and Scutellariae Radix resulted in significant increase in AUC0-2880 and MRT of oral MTX and even led to death. However, substantially no effect was observed for intravenous MTX. It seems prudent to avoid the concurrent use of Rhei Rhizoma or Scutellariae Radix herbal remedies containing them.
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