Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/1816
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    標題: 以體外及體內試驗研究多重抗藥性抑制劑對抗癌藥物運送之影響
    The Effects of Multidrug Resistance Reversing Agents on the Uptake Distribution and Efflux of Anticancer Drugs: In Vitro, in Situ and in Vivo Studies
    作者: 駱雨利
    Yu-Li Lo
    貢獻者: 藥學系
    關鍵字: P-醣蛋白
    共軛焦雷射掃描顯微鏡
    流動細胞計數法
    抗腫瘤藥
    多重抗藥性
    泛艾黴素
    維拉巴米
    P-glycoprotein
    Confocal laser scanning microscope
    Flow cytometer
    Antitumor drug
    Multidrug resistance (MDR)
    Epirubicin
    Cremophor EL
    Verapamil
    Trifluoperazine
    日期: 1998
    上傳時間: 2008-07-18 16:08:01 (UTC+8)
    出版者: 台南縣:嘉南藥理科技大學藥學系
    摘要: 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。使用流式細胞分析儀分析發現Cremophor EL,Verapamil或Trifluoperazine均明顯增進Epirubicin於Caco-2癌細胞之積聚。我們使用老鼠小腸以評估Cremophor EL,Verapamil或Trifluoperazine是否可促進Epirubicin於小腸之吸收。結果顯示不管是在空腸或迴腸,此三個P醣蛋白抑制劑均能明顯增進Epirubicin之吸收。以人類結腸腺癌細胞為模型,發現此三個抑制劑可促進Epirubicin於吸收方向之運輸及減少Epirubicin於排出方向之運輸。總結, Cremophor EL、Verapamil及Trifluoperazine為有效之多重抗藥性抑制劑,但Cremophor EL於臨床使用之可能性較大,因其具有無全身性副作用之優點並能以體內試驗可用之濃度以增加Epirubicin於小腸之吸收。而具有促進Epirubicin生體可用率之潛力。
    P-glycoprotein (P-gp) actively pumps out a number of anticancer drugs, such as epirubicin, from tumor cells. Inhibition of intestinal P-gp function using MDR reversing agents may enhance oral bioavailability of some chemotherapeutic agents. Our previous flow cytometric study showed that Cremophor EL, verapamil or trifluoperazine all increased the intracellular accumulation of epirubicin in Caco-2 cells. In this study, the effect of Cremophor EL, verapamil or trifluoperazine as MDR reversing agents on the enhancement of intestinal absorption of epirubicin was investigated in both everted gut sacs of rats and human intestinal epithelial Caco-2 cell layers. The epirubicin concentrations measured in everted gut sacs pretreated with either of these modulators were significantly higher than those in epirubicin control in both the jejunum and the ileum. The addition of these modulators significantly increased apical-to-basolateral flux and reduced basolateral-to-apical flux of epirubicin across Caco-2 cells. In conclusion, our results demonstrated that Cremophor EL, verapamil or trifluoperazine are potent MDR modifiers of epirubicin. However, Cremophor EL has the advantage of no systemic side effects. Use of Cremophor EL as excipient may increase intestinal absorption of epirubicin and thus improve bioavailability of epirubicin
    關聯: 計畫編號:NSC87-2314-B041-008
    显示于类别:[藥學系(所)] 科技部計畫

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