併服富含多酚中藥對西藥滅殺除癌（Methotrexate）動力學之影響

中國醫藥大學機構典藏 China Medical University Repository, Taiwan > 藥學院 > 藥學系暨碩博士班 > 研究計畫 > Item 310903500/13575

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题名:	併服富含多酚中藥對西藥滅殺除癌（Methotrexate）動力學之影響
其它题名:	Effect of Polyphenol-Rich Chinese Herbs on the Pharmacokinetics of Methotrexate
作者:	李珮端(Pei-Dawn Lee Chao);徐素蘭(Hsiu,Su-Lan);侯鈺琪(Hou,Yu-Chi)
贡献者:	藥學院藥學系
关键词:	多酚;滅殺除癌;中西藥交互作用;polyphenol;methotrexate;pharmacokinetics
日期:	2004-12-31
上传时间:	2009-09-01 16:25:05 (UTC+8)
摘要:	多酚類化合物廣泛存在於各種中藥及蔬果中，同時亦是近年坊間風行的健康食品。體外細胞株的研究顯示，多酚類具調控體內藥物運送蛋白之活性。滅殺除癌（Metrothexate）為一重要的西藥，廣泛的用於類風濕關節炎、牛皮癬、抗癌等，但治療指數非常狹窄，是抗癌西藥中必需進行血中濃度監測的唯一藥物。其不良反應影響胃、肝及中樞系統。許多研究顯示，多酚類化合物主要以硫酸及葡萄糖醛酸結合態代謝物循環於血流中，近來更發現其外排與MRP2、MRP3等運送蛋白有關，而滅殺除癌之外排則與MRP1、MRP2、MRP3、MRP4等運送蛋白有關。吾人臆測多酚類與滅殺除癌併服時會競爭MRP2及MRP3，導致體內之交互作用。迄今文獻中並無有關中藥與滅殺除癌動力學交互作用之報導。因此，本研究擬以大白鼠為模型，探討富含多酚中藥對滅殺除癌動力學之影響。本計畫擬利用交叉設計，予大白鼠分別單獨口服滅殺除癌及分別併服大黃、黃芩與葛根水煎劑，定時自心臟穿刺採血，滅殺除癌之血中濃度以螢光偏極免疫測定法定量。血中藥物濃度數據以WINNONLIN軟體計算動力學參數，並以paired Student’s t- test 統計組間差異。本研究預期可了解併服富含多酚中藥對體內滅殺除癌之血中動態學之影響，對長期服用滅殺除癌病患之臨床療效或安全極具參考價值。 Polyphenols are widely distributed in Chinese herbs and vegetables. In recent years, Polyphenol has become popular dietary supplements worldwide. The in vitro studies showed that polyphenols possessed activity to modulate the function of drug transporters. Methotrexate is an important western medicine, which is mainly used in curing rheumatoid arthritis, psoriasis and anticancer. However, the therapeutic window is very narrow. Methotrexate is the only anticancer drug that requires therapeutic monitoring of blood level. Its side effects would affect stomach, liver and central nervous system. Many researches showed that polyphenols are mainly presented in the blood stream as conjugated metabolite e.g. sulfates and glucuronides. Recent finding even shows that its elimination is related to MRP2 and MRP3 transporter. However, the elimination of methotrexate is associated with MRP1, MRP2, MRP3 and MRP4 transporters. We may therefore speculate that polyphenol and methotrexate would compete for MRP2 and MRP3, and lead to drug interaction in vivo. Till now, no report concerned about pharmacokinetic interaction between Chinese herbs and methotrexate is being reported. Hence, in this proposal, we will use rats as our model to investigate the pharmacokinetic effects of polyphenol ？HHV containing Chinese herbs, on the pharmacokinetics of methotrexate. Crossover design will be conducted to administer rats with methotrexate orally, and coadminister decoctions of Da-Huang, Huang-Chin and Ger-Gen, respectively. Blood samples will be withdrawn via cardiopuncture. The concentration of methotrexate in blood will be determined by FPIA method. The pharmacokinetics parameters would be calculated by WINNOLIN. Paired-Student？HH？HHs t-test will be used to for statistical comparison between the groups. Through this research. We anticipate to understand more about the pharmacokinetic effects of polyphenol ？HHV containing Chinese herbs on the biological fates of methotrexate. It would provide important information for clinical use of methotrexate to ensure the safety of patients.
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