Disposition kinetics of adriamycin, adriamycinol and their 7-deoxyaglycones in AKR mice bearing a sub-cutaneously growing ridgway osteogenic sarcoma (ROS).
Disposition kinetics of Adriamycin (ADR), adriamycinol (AOL) and their 7-deoxyaglycones (ADR-DONE and AOL-DONE) have been studied in AKR mice bearing a s.c. growing ROS tumour after i.v. administration of 10 mg/kg. ADR and its metabolites were extracted from tissues by two different methods, separated and identified by HPLC. Tissue 7-deoxyaglycones were isolated, purified and then identified by HPLC, TLC and mass spectrometry. Kinetic profiles of ADR showed rapid equilibration of the drug with well perfused tissues but a slower and complex equilibration of the drug with the ROS tumour. Serum and tissue profiles of AOL were similar to the parent drug. From the kinetic profiles of the 7-deoxyaglycones it appeared that in the tissues their formation was rapid, with ADR-DONE always appearing first. Maximum concentrations of ADR-DONE were reached in the liver and heart only 10 min after drug administration. Estimated half lives of ADR-DONE were in liver, 1.1 hr and in heart, 2.8 hr and for AOL-DONE in liver, 5.4 hr, in heart, 5.1 hr and in serum, 4.1 hr.
Cummings
J
J
Merry
S
S
Willmott
N
N
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D051379:Mice; D008806:Mice, Inbred AKR; D009206:Myocardium / Q000378:metabolism; D009279:Naphthacenes / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism*
D009279:Naphthacenes; C049327:7-deoxyadriamycinol aglycone; D004317:Doxorubicin; C010013:adriamycinol; C049326:7-deoxyadriamycin aglycone