Studies on the Absorption, Distribution, Metabolism, and Excretion of Propionylmaridomycin in Rats

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The absorption, distribution, metabolism, and excretion of propionylmaridomycin was investigated in the rat by using [14C]propionylmaridomycin. Propionylmaridomycin was absorbed from the gastrointestinal tract at a relatively rapid rate and was readily distributed into tissues. Among the tissues examined, liver, kidney, and lung showed a remarkably higher level of the radioactivity than plasma, while distribution of the radioactivity into brain was little. However, a significant accumulation of the radioactivity in tissues was not observed. Excretion of the radioactivity was mainly via the fecal route and the high fecal recovery was accounted for by unabsorbed drug and biliary excretion of the drug and/or its metabolites. Tissue distribution of antimicrobial activity was also investigated and lung was found to show the highest antimicrobial activity among any tissues examined. Propionylmaridomycin was completely converted to several metabolites by the rat and the presence of at least three components was confirmed as biologically active metabolites. Of these metabolites, 4″-depropionyl-9-propionylmaridomycin was identified, which was the major metabolite in tissues, plasma, and urine.

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