P-glycoprotein(P-gp) actively pumps out a number of anticncer drugs, such as epirubicin, from tumor cells.P-gp also expresses in the snall intestine at normal physiological conditions.Inhibition of instestinal P-gp function using MDR reversing agents may enhance oral bioavailabil-ity of some chemotherapeutic agents. Cremophor EL is a pharmacologically inert surfactant and has the advantage of no systemic side effect. Our previous flow cytometric study showed that Cremophor EL might have MDR reversing effects and increased the increased the intracellular accumulation of epirubicin in Caco-2 cells. In this study, the effect of Cremophor EL as a MDR reversing agent on the enhancement of intestinal absorption of epirubicin was investigated in both everted gut sacs of rats and human intestinal epithelial Caca-2 cell layers. The epirubicin concentrations measured in everted gut sacs pretreated with cremophor EL were significantly higher then those in epirubicin control for both the jejunum and the ileum. The addition of Cremophor EL significantly increased apical-to-basolateral permeability and reduced basolateral-to-apical permeability of epirubicin across Caca-2 cells. In conclusion, our results demonstrate that Cremophor EL is a potent MDR modifier of epirubicin in both human colon adenocarcinoma cells and everted gut sacs of rats at concentration that could be achieved in vivo. Use of Cremophor EL as excipient may increase intestinal absorption of some drugs through the mechanism of P-gp inhibition and thus improve drug bioavaiability for P-gp substrates. P醣蛋白可排出許多抗癌藥物，因而降低抗癌藥物例如Epirubicin之療效。如能使用多重抗藥性抑制劑抑制小腸P醣蛋白之功能，將有助於促進Epirubicin之生體可用率。Cremophor EL為一無藥理活性之界面活性劑，具有無全身性副作用之優點。我們之前使用流式細胞分析儀分析，發現Cremophor EL明顯增進Ep irubicin於Caco-2癌細胞之積聚。因此在考篇研究中，我們使用老鼠小腸及人類結腸腺癌細胞以評估Cremophor EL是否可促進Ep irubicin於小腸之吸收。實驗結果顯示，不管是在空腸或迴腸，Cremophor EL均能明顯增進Epirubicin之吸收。以人類結腸腺癌細胞為模型，發現Cremophor EL可促目進Epirubicin於吸收方向之運輸及減少Epirubicin於排方向之運輸。總結，實驗結果顯示Cremophor EL為有效之多重抗藥性抑制劑，能以體內試驗可用之濃度以促進抗癌藥物Epirubicin於老鼠小腸之吸收及結腸腺癌細胞.運輸。使旋用Cremophor EL於賦形劑中可以經由抑制P醣蛋白之機轉以促進藥物之小腸吸收，並增進P醣蛋白受質之生體可用率。
