Enhanced cardiotoxicity in rabbits treated with verapamil and adriamycin.
Verapamil, a calcium channel blocker, reduces resistance of some tumors to Adriamycin by inhibiting Adriamycin efflux from resistant cells. This study shows that rabbits given 7 mg/kg of Adriamycin and 0.8 mg/kg of verapamil died earlier with functional and morphological cardiac abnormalities than rabbits given Adriamycin alone. Rabbits that were given verapamil and died peracutely had higher concentrations of Adriamycin in the myocardium. The relatively high dose of Adriamycin was expected to produce cardiotoxicity in rabbits within a matter of days. However, peracute death (within hours) in rabbits given the same dose of Adriamycin but with verapamil treatment was unexpected. These results suggest that combining Adriamycin with verapamil increases early cardiac toxicity. Therefore, clinical use of this combination should be approached cautiously until the interactions, including the possibility for enhanced normal tissue damage, are fully understood.
Stephens
L C
LC
Division of Veterinary Medicine and Surgery, University of Texas, MD Anderson Hospital and Tumor Institute, Houston.
Wang
Y M
YM
Schultheiss
T E
TE
Jardine
J H
JH
D000818:Animals; D004317:Doxorubicin / Q000032:analysis / Q000633:toxicity*; D004357:Drug Synergism; D006321:Heart / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000032:analysis / Q000473:pathology; D011817:Rabbits; D014700:Verapamil / Q000633:toxicity*
D004317:Doxorubicin; D014700:Verapamil