THE DISPOSITION OF THE NEW ANTHRACYCLINE ANTIBIOTIC, MENOGAROL, IN MICE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 12  (3) , 365-370
Abstract
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 [high performance liquid chromatography]. Plasma concentrations of 7-OMEN declined in triexponential fashion. The terminal t1/2 [half-life] was 10.6 h, the AUC [area under the concentration-time curve] was 10.13 .mu.M .times. h; the apparent Vc [volume of central compartment] 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.