Disposition and metabolism of adriamycin in the rat

Adriamycin (ADR) is extensively excreted in bile and moderately in urine following its administration to anesthetized rats. At intravenous doses ranging from 5 to 20 mg/kg, approximately 34% of the injected ADR is excreted in bile as total drug equivalents and 6-8% in urine over a 10-hour period. Thin-layer chromatography of bile, urine and tissue extracts revealed the presence of three major metabolic products in addition to the parent drug. In either bile or urine, unchanged ADR was the predominant form excreted and accounted for about 70% of the total drug equivalents. Adriamycinol and ADR conjugates were the major metabolites, were excreted at comparable rates and together accounted for most of the remaining fluorescence or radioactivity in either body fluid. ADR itself was the main form found in all tissues examined. ADR conjugates were not detected in any tissue whereas adriamycinol was observed in kidney, heart and spleen, but not in the liver. ADR aglycones could not be detected in the heart. They appeared preferentially in the liver where, 3 h after ADR was injected, they accounted for about 40% of total tissue fluorescence or radioactivity. The low rate of ADR conversion observed in the present studies supports the hypothesis of species difference in the metabolism of the drug.