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題名 | 併服富含多酚中藥對西藥滅殺除癌(Methotrexate)動力學之影響=Effect of Polyphenol-Rich Chinese Herbs on the Pharmacokinetics of Methotrexate |
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作者 | 李珮端; | 書刊名 | 中醫藥年報 |
卷期 | 25:1 2007.10[民96.10] |
頁次 | 頁181-206 |
專輯 | 中醫藥療效評估之研究 |
分類號 | 414.33 |
關鍵詞 | 多酚; 滅殺除癌; 交互作用; 大黃; 黃芩; 葛根; Polyphenol; Methotrexate; Herb-drug interaction; Rhubarb; Scutellariae radix; Puerariae radix; |
語文 | 中文(Chinese) |
中文摘要 | 滅殺除癌(Methotrexate, MTX)為一重要的西藥,用於類風濕關節炎、牛皮癬、抗癌等,但治療指數非常狹窄,是抗癌西藥中必須進行血中濃度監測的唯一藥物。MTX之外排與MRP1、MRP2、MRP4等運送蛋白有關。其不良反應包括肝、血液、胃及肺毒性。 近年來,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,最近更發現其外排與MRP1、MRP2、MRP3等運送蛋白有關,吾人臆測多酚類與MTX併服時可能會競爭MRP1、MRP2及MRP3等,而導致動力學交互作用。 本研究以大白鼠為模型,利用平行設計,單獨口服MTX及分別併服大黃、黃芩與葛根水煎劑,定時自心臟穿刺採血,MTX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ANOVA統計組間差異。 MTX併服大黃、黃岑及葛根後,平均血藥面積分別顯著增加了199.0%、178.2%與202.7%;而平均滯留時間則增加了199.3%、170.5%與237.8%。另外,併服大黃、黃岑及葛根亦顯示增高了大鼠之死亡率。 本研究結果顯示併服富含多酚之中藥顯著抑制MTX從體內排出,對服用MTX病患可能造成毒性,建議避免併服,以確保用藥安全。 |
英文摘要 | Methorexate (MTX) is a potent anticancer agent with narrow therapeutic range and also used to treat psoriasis and rheumatoid arthritis. MRP1, MRP2, MRP3 and MRP4 are related with the transport of MTX. Serious adverse effects of MTX include hepatic, hematologic, gastric and pulmonary toxicity. Most polyphenols were known to present as conjugated metabolites in circulation including glucuronides and sulfates that were associated with transporters MRP1, MRP2 and MRP3. We proposed that polyphenols may compete for MRP1, MRP2 and MRP3 with MTX and resulted in pharmacokinetic interaction. This study investigated the effects of decoctions of Rhubarb (Rheum palmatum LINN), Scutellariae Radix (Scutellaria baicalensis GEORGI), and Puerariae Radix (Pueraria lobata (Wild.) OHWI.) on MTX pharmacokinetics. Four groups of rats (n=6-8) were studied in parallel design. Following an overnight fast, rats were given MTX 5.0 mg/kg orally either with water or with decoctions of Rhubarb, Scutellariae Radix and Puerariae Radix, respectively. Blood samples withdrawn via cardiopuncture were assayed for MTX by a specific monoclonal FPIA method. Non-compartment model of WINNONLIN was used for the computation of pharmacokinetic parameters. ANOVA was used for satistical comparison of pharmacokinetic parameters among groups taking P<0.05 as significant. After coadminstrations of decoctions of Rhubarb, Scutellariae Radix and Puerariae Radix, the mean AUC0-2880 of MTX were significantly increased by 199.0%, 178.2% and 202.7%, respectively, the mean MRT of MTX were significantly increased by 199.3%, 170.5% and 237.8%, respectively. In addition, coadminisration of Rhubarb, Scutellariae Radix and Puerariae Radix markedly enhanced the mortality in rats. In conclusion, coadminstration of polyphenol-rich herbs with MTX resulted in significant inhibition on the elimination of MTX and led to higher toxicity. It seems prudent to avoid the concurrent use of herbal remedies containing polyphenols with MTX. |
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