Comparative mammalian metabolism of adriamycin and daunorubicin.

Abstract Both Adriamycin and daunorubicin undergo carbonyl reduction and glycosidic cleavage. We have investigated kinetic parameters of these reactions with several mammalian species including humans. Adriamycin and daunorubicin showed similar K m values for reduction in all organs studied except those from rabbits. Both rabbit liver and kidney have a much lower K m for Adriamycin reduction. In contrast to the great similarity in K m 9s, the V max 9s varied greatly according to drug, organ, and species. Daunorubicin showed a greater V max than did Adriamycin in all organs studied. The V max ratio of daunorubicin to Adriamycin ranged from 159 to 178 in mice and rats to 10 to 30 in humans. Liver and kidney always showed greater activity than did cardiac or skeletal muscle. These enzymatic data correlate with the quicker in vivo reduction of daunorubicin than of Adriamycin, with a greater percentage of daunorubicin than Adriamycin excreted in the reduced form, than and, inversely, with clinical efficacy in that Adriamycin has a wider spectrum of antitumor activity. All organs showed high levels of glycosidic cleavage in the absence of oxygen. In vivo , relatively little of either Adriamycin or daunorubicin is in the aglycone form. Thus, tissues, especially liver, have a great potential for glycosidic activity that is normally not exhibited. However, in certain patients this may be an important mechanism of biotransformation. Although the role of these activities in normal cellular physiology is unknown, their ubiquity points toward an essential function.