The murine metabolism and disposition of marcellomycin

The metabolism and disposition of marcellomycin (MCM), a new anthracycline antitumor antibiotic, were studied after iv administration to mice. In plasma, total drug fluroescence decreased according to first order kinetics and was mainly comprised of parent drug. In addition to MCM, five compounds (M2, P1, P2, G1, G2) were seen. M2 reflected the presence of a contaminant in the parent drug. P1 and P2 represented polar conjugates of MCM and M2, respectively; and G1 and G2 proved to be aglycones. P1 and G1 were observed during the first hours after injection, and G2 was more persistent and represented 35-50% of total drug fluorescence by 8 hr after injection. MCM was distributed widely to organs, except the brain. High MCM concentrations were measured in the lungs initially but they decreased quickly and, by 60 min, reached values similar to those present in the liver and kidneys. Low MCM concentrations were observed in heart and muscles. The splenic concentration of fluorescence rose progressively and, by 16 hr, was higher than that in all other organs. The concentrations of MCM metabolites were small in all tissues except in the liver, where an aglycone identified as 7-deoxypyrromycinone, was seen during the first 4 hr after injection. Our results indicate that the metabolism of MCM in the mouse is qualitatively similar to that in man, but that important quantitative differences exist. The significance of this observation as a possible explanation of the differences in observed toxicities between the two species remains to be established.