Chauffert B, Rey D, Coudert B, Dumas M, Martin F
INSERM, Unite 252, Faculty of Medicine, Dijon, France.
Br J Cancer. 1987 Aug;56(2):119-22. doi: 10.1038/bjc.1987.167.
We have previously demonstrated that amiodarone is able to reverse resistance of rat colon cancer cells to anthracyclines. We now compare the efficiency of amiodarone to verapamil one, another antiarrhythmic agent used in experimental systems and in clinical trials to enhance the effects of anthracyclines on resistant cancer cells. Amiodarone is more efficient than verapamil when both drugs are used at the same molar concentrations. Desethylamiodarone, the main metabolite of amiodarone, is as efficient as its precursor. Optimal concentrations of amiodarone are obtained without side effects in the sera of patients treated by oral administration followed by a loading infusion of amiodarone. On the other hand, maximal tolerated levels of verapamil reported in clinical trials are less efficient than amiodarone maximal levels in the reversal of resistance to anthracyclines in our experimental model in vitro. We suggest that amiodarone, which is more efficient and less toxic than verapamil, could be substituted for verapamil in future clinical trials.
我们之前已经证明,胺碘酮能够逆转大鼠结肠癌细胞对蒽环类药物的耐药性。我们现在比较胺碘酮与维拉帕米的效果,维拉帕米是另一种用于实验系统和临床试验的抗心律失常药物,用于增强蒽环类药物对耐药癌细胞的作用。当两种药物以相同摩尔浓度使用时,胺碘酮比维拉帕米更有效。胺碘酮的主要代谢产物去乙基胺碘酮与其前体的效果相同。通过口服给药随后静脉滴注负荷剂量的胺碘酮治疗的患者血清中,可获得无副作用的胺碘酮最佳浓度。另一方面,在我们的体外实验模型中,临床试验中报道的维拉帕米最大耐受水平在逆转对蒽环类药物的耐药性方面不如胺碘酮的最大水平有效。我们建议,在未来的临床试验中,比维拉帕米更有效且毒性更小的胺碘酮可以替代维拉帕米。