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Journal of Pharmacology And Experimental Therapeutics, Vol. 191, Issue 2, 331-340, 1974
Copyright © 1974 by American Society for Pharmacology and Experimental Therapeutics

ADRIAMYCIN AND DAUNORUBICIN DISPOSITION IN THE RABBIT

N. R. Bachur 1, R. C. Hildebrand 1, and R. S. Jaenke 1

1 Biochemistry Section, Baltimore Cancer Research Center, DCT, NCI, NIH, Baltimore, Maryland and Department of Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado

Rabbits, animals which develop a cardiotoxicity from adriamycin (A) and daunorubicin (D), excrete about 17% of intravenously injected A on D via their bile and only 2% of the drugs in their urine for 8 hours after administration as measured by drug fluorescence. Thin-layer analysis of bile and urine indicates extensive metabolism of A and D, principally the carbonyl reduction of both, to adriamycinol and daunorubicinol, respectively. Generally D is metabolized more than A. Other polar metabolites, presumably conjugates, are the next most prevalent group of metabolites. Tissues contain higher levels of D than A and substantial quantities of reduced metabolites of both. Free aglycone metabolites are not prominent except in liver, kidney and small intestine. No unusual metabolite or high drug on metabolite levels are found in the heart to account for the cardiotoxicity. Homogenates and soluble fractions of rabbit liver and kidney metabolize both adriamycin to adriamycinol and daunorubicin to daunorubicinol with a dependence on reduced triphosphopyridine nucleotide. Isolated adriamycinol was identified by comparative thin-layer chromatography and ultraviolet-visible, infrared and mass spectroscopy.

Submitted on March 22, 1974
Accepted on July 8, 1974




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