The disposition of the new anthracycline antibiotic, menogarol, in mice.
We have investigated the metabolism and disposition, in mice, of 7-con-O-methylnogarol ( menogarol ; 7-OMEN), a new anthracycline antibiotic entering clinical trials. 7-OMEN, dissolved in 0.01 M glucuronic acid, was administered iv to mice (10 mg/kg). At specified times after injection, groups of mice were killed and 7-OMEN and metabolites were assayed in plasma and organs by HPLC. Plasma concentrations of 7-OMEN declined in triexponential fashion. The terminal t1/2 was 10.6 hr; the AUC was 10.13 microM X hr; the apparent Vc was 0.4 liter/m2, and the systemic clearance was 91.2 ml/min/m2. One metabolite, with the same HPLC characteristics as N- demethylmenogarol , was seen in plasma during the first 30 min after injection. 7-OMEN was distributed extensively to all tissues except brain. Initially, pulmonary concentrations of 7-OMEN were 15 times higher than those in any other organ and 30 times higher than those in plasma. Concentrations of 7-OMEN were the most persistent in spleen, kidney, and pancreas, and the least persistent in heart and liver. The AUC for 7-OMEN in organs was the greatest in lungs (605 nmol/g X hr), spleen (522 nmol/g X hr), and pancreas (430 nmol/g X hr), and least in heart (33 nmol/g X hr) and liver (60 nmol/g X hr). Kidneys and skeletal muscles had intermediate AUC values. In liver, two metabolites, one of which had the HPLC characteristics of N- demethylmenogarol , were seen. In other organs, the same metabolites were seen later and in small quantities.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000097:blood / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003630:Daunorubicin / Q000031:analogs & derivatives*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D017290:Menogaril; D051379:Mice; D009621:Nogalamycin / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D000903:Antibiotics, Antineoplastic; D017290:Menogaril; D009621:Nogalamycin; D003630:Daunorubicin