Cardiotoxicity from the antitumor anthracycline, doxorubicin, correlates with cardiac drug levels, redox activation, and formation of the metabolite doxorubicinol. The cardiotoxicity may first be observed during salvage therapy with other drugs such as the anthracenedione mitoxantrone. In contrast, less cardiac toxicity has been observed in patients treated with doxorubicin followed by the anthracenedione pixantrone. In doxorubicin-pretreated human myocardial strips, pixantrone or mitoxantrone did not alter levels of residual doxorubicin. Mitoxantrone showed an unchanged uptake but synergized with doxorubicin for more redox formation. In contrast, pixantrone uptake was reduced, lacked redox synergism with doxorubicin, and inhibited formation of doxorubicinol.
See article at J Pharmacol Exp Ther 2013, 344:467–478.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics