THE MURINE METABOLISM AND DISPOSITION OF MARCELLOMYCIN

  • 1 January 1984
    • journal article
    • research article
    • Vol. 12  (2) , 209-216
Abstract
The metabolism and disposition of marcellomycin (MCM) [from Actinosporangium], a new anthracycline antitumor antibiotic, were studied after i.v. administration to mice. In plasma, total drug fluorescence decreased according to first order kinetics and comprised mainly parent drug. In addition to MCM, 5 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. 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 h 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 h, 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 h after injection. The metabolism of MCM in the mouse is evidently qualitatively similar to that in man, but important quantitative differences exist. The significance of this observation as a possible explanation of the differences in observed toxicities between the 2 species remains to be established.