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含黃酮類中藥與地高辛（Digoxin）之動態學交互作用研究（I） 侯鈺琪中國醫藥學 |
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| 黃酮類是天然的多酚類化合物，廣泛存在於各種中藥或蔬果中。槲皮素及其配醣體為廣泛分布於許多中藥的常見黃酮類成分。槲皮素是芸香的非醣體，在中藥槐米中含有大量的芸香。口服後之芸香必須被腸道細菌水解成槲皮素後方能吸收。近年來發現槲皮素具有強力之抗腫瘤、抗氧化及抗發炎活性，目前正在進行抗癌臨床試驗，而且是常見的健康食品。另外微粒體的體外研究顯示檞皮素為強力之CYP 3A4抑制劑。許多細胞株的研究則發現檞皮素顯著地影響p-glycoprotein (Pgp)之活性。地高辛（Digoxin）為一重要的強心配糖體藥物，但治療指數非常狹窄。任何會改變地高辛血中濃度之因素，皆會造成臨床治療上重大的不良反應。 Pgp與CYP 3A4 為腸道與肝對外來物吸收之屏障。Digoxin為Pgp之受質，迄今文獻中並無有關中藥槐米及檞皮素與地高辛動態學交互作用之研究報導。因此，本研究擬以豬為模型，探討中藥對地高辛動態學之影響。本計畫擬利用交叉設計將豬分別單獨灌食地高辛或併服中藥，定時自豬頸靜脈採血，地高辛之血中濃度以特異性之單株抗體螢光偏極免疫測定法定量血中濃度。若發現有中藥可降低地高辛之血中濃度，則可再進一步評估開發其成為地高辛解毒劑之可行性。同時本計畫亦擬藉由翻腸之體外實驗，探討交互作用產生之機轉。本研究預期應可瞭解中藥槐米及廣泛存在的檞皮素與地高辛間之動態學交互作用，觀察其對地高辛血中濃度的影響。此研究對地高辛與中藥臨床併用之療效或安全性極具參考價值。 | |
| 關鍵字：槐花、中藥、檞皮素，地高辛，中西藥物交互作用、P-醣蛋白 |
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The Influence of Flavonoid-Containing Chinese Herbs on Digoxin Pharmacokinetics(I) Hou Yu ChiChina medical college |
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| Quercetin and rutin are common constituents in daily diet and Chinese herbs. Rutin is a glycoside of quercetin which is the absorbable form after hydrolysis by enteral microflora. In recent years it was shown that quercetin had potent anticarcinogenic, antioxidative and anti-inflammatory capacities. It is currently in phase I clinical trial. Microsome studies reported that quercetin was a potent CYP 3A4 inhibitor. Many cell line studies indicated that quercetin significantly modulate p- glycoprotein (Pgp), however, the result showing that quercetin stimulated or inhibited the efflux of Pgp substrates was still a discrepancy and is yet unexplained. Whether quercetin is a substrate of Pgp or not is still controversial. Digoxin is an important cardiac glycoside with narrow therapeutic index. Any factor alters its blood level would result in important clinical consequences. Digoxin is a substrate of Pgp and CYP 3A4 in rat and a substrate of Pgp in humans. Both Pgp and CYP 3A4 are barrier f | |
| 關鍵字：rutin, quercetin, digoxin , drug interaction |
