Tween 80 increases plasma adriamycin concentrations in mice by an apparent reduction of plasma volume

S.D. Harrison Jr. , A.M. Cusic, S.M. McAfee
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引用次数: 14

Abstract

Coadministration of Tween 80 enhances the activity of adriamycin against selected experimental tumors in mice. Although some investigators have suggested a direct effect of Tween 80 on tumor cells, we wished to determine whether altered plasma concentrations of adriamycin occurred which might account for the apparent therapeutic synergism. Male CDF1 mice were treated i.p. with 6.7 mg/kg of adriamycin alone or combined with 5000 mg/kg of Tween 80 in physiologic saline. Fluorometric determination of adriamycin equivalents in plasma revealed significantly higher adriamycin concentrations 1 and 2 hr post treatment in mice that had received Tween 80. In three separate experiments, a significant, reversible increase in packed cell volume occurred in the peripheral blood of mice treated i.p. with Tween 80. This increase was maximal at 1–2 hr post treatment. The magnitude of the apparent plasma volume reduction accounted quantitatively for the increase in drug concentration.

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t80通过明显减少血浆体积增加小鼠血浆中阿霉素浓度
t80可增强阿霉素对小鼠肿瘤的抑制作用。虽然一些研究者认为Tween 80对肿瘤细胞有直接作用,但我们希望确定阿霉素的血浆浓度是否发生了改变,这可能解释了明显的治疗协同作用。雄性CDF1小鼠分别单独给予6.7 mg/kg阿霉素或在生理盐水中联合给予5000 mg/kg Tween 80。血浆中阿霉素当量的荧光测定显示,在给予Tween 80的小鼠治疗后1和2小时,阿霉素浓度显著升高。在三个单独的实验中,用Tween 80处理的小鼠外周血中填充细胞体积显著可逆地增加。这种增加在治疗后1-2小时达到最大。表观血浆体积减少的幅度定量地说明了药物浓度的增加。
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