Metabolism of the anthracycline antibiotic daunorubicin to daunorubicinol and deoxydaunorubicinol aglycone in hepatocytes isolated from the rat and the rabbit.
In the rat and rabbit hepatocyte in suspension, daunorubicin was metabolized primarily to deoxydaunorubicinol aglycone and daunorubicinol. Little deoxydaunorubicin aglycone was observed in either species. High levels of daunorubicinol in the rabbit hepatocyte reflected the greater affinity of rabbit hepatic aldo-keto reductase for the substrate, daunorubicin. Conjugates of the anthracyclines were not observed with hepatocytes from either species. The relative formation of deoxydaunorubicinol aglycone and deoxydaunorubicin aglycone suggests that daunorubicinol is a preferred substrate for reductive deglycosidation. Consequently, the presence of daunorubicinol in the circulation of patients undergoing chemotherapy with daunorubicin may be a factor in the therapeutic efficacy of this antineoplastic agent.
D000818:Animals; D001663:Bilirubin / Q000031:analogs & derivatives / Q000378:metabolism; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D009279:Naphthacenes / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D009279:Naphthacenes; C016266:bilirubin glucuronate; C035451:7-deoxy-13-dihydrodaunorubicinone; D001663:Bilirubin; C000847:daunorubicinol; D003630:Daunorubicin