Metabolism and Disposition of Menogaril (NSC 269148) in the Rabbit1

We have investigated the metabolism and disposition, in rab bits, of menogaril (7-OMEN), a new anthracycline antibiotic re cently introduced into clinical trials. 7-OMEN was administered by rapid i.v. injection at a dosage of 2.5 mg/kg. 7-OMEN and metabolites were assayed by high performance liquid chromatography. Plasma concentrations of 7-OMEN declined in biexponential fashion with a terminal half-life of 2.7 h. The area under the plasma concentration versus time curve was 1.3 U,Mx h. The systemic clearance of 7-OMEN was 57.6 ml/min/kg. No metabolite of 7-OMEN was detected in plasma. At 8 h after treatment, the cumulative urinary and biliary excretions of 7OMEN equivalents amounted to 1.3 and 3.4% of the total administered dose, respectively. 7-OMEN was the predominant fluorescent compound in urine, but four metabolites were also seen. In bile, 7-OMEN represented only 9.6% of the cumulative excretion and six metabolites were observed. Among the organs, lungs contained the highest concentrations of parent drug. Sub stantial concentrations of metabolites were observed in the kidneys, liver, duodenum, and small intestine. Three of the observed metabolites of 7-OMEN have been tentatively identified as A/-demethylmenogaril, 7-deoxynogarol, and A/-demethyl-7deoxynogarol.