The disposition of the new anthracycline antibiotic, menogarol, in mice
Dodion, P.; Chang, B.K.; Egorin, M.J.; Olman, E.A.; Engisch, K.L.; Bachur, N.R.
Drug Metabolism and Disposition the Biological Fate of Chemicals 12(3): 365-370
1984
ISSN/ISBN: 0090-9556 PMID: 6145565 Document Number: 230291
The metabolism and disposition, in mice, of 7-con-O-methylnogarol (menogarol; 7-OMEN), a new antitumor anthracycline antibiotic entering clinical trials, were investigated. 7-OMEN, dissolved in 0.01 M glucuronic acid, was administered i.v. 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 was 0.4 l/m2; and the systemic clearance was 91.2 ml/min per 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 .times. h) spleen (522 nmol/g .times. h and pancreas (430 nmol/g .times. h), and least in heart (33 nmol/g .times. h) and liver (60 nmol/g .times. h). Kidneys and skeletal muscles had intermediate AUC values. In liver, 2 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.