Amiodarone is more efficient than verapamil in reversing resistance to anthracyclines in tumour cells.
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.
Chauffert
B
B
INSERM, Unite 252, Faculty of Medicine, Dijon, France.
Rey
D
D
Coudert
B
B
Dumas
M
M
Martin
F
F
D000230:Adenocarcinoma / Q000188:drug therapy; D000638:Amiodarone / Q000627:therapeutic use*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D002460:Cell Line; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004351:Drug Resistance; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D051381:Rats; D014700:Verapamil / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D014700:Verapamil; D000638:Amiodarone; C030851:esorubicin