Inhibition of drug oxidation and stimulation of NADPH oxidase in vitro by doxorubicin and triferric-doxorubicin.

The electrophilic properties of the quinone-hydroquinone configuration of anthracycline antibiotics suggests a possible influence on cytochrome P-450-mediated mono-oxygenase reactions. Both doxorubicin and triferric-doxorubicin (a derivative in which the quinone groups are blocked with iron) showed a similar dose-dependent inhibition of liver microsomal drug metabolism. A doxorubicin concentration-related stimulation of NADPH oxidase activity was found to be linear but that for triferric-doxorubicin was asymptotic. Neither inhibitor affected the activity of cytochrome c reductase, cytochrome b5 reductase or cytochrome P-450 reductase. However, doxorubicin did potentiate the inhibitory effect of aniline on cytochrome P-450 reductase and on ethylmorphine metabolism. It is concluded that these anthracyclines inhibit drug metabolism in vitro not by their electron-withdrawing potential but in a manner more similar to that described for type II compounds.