RT Journal Article SR Electronic T1 Elimination Pathways of [14C]Losoxantrone in Four Cancer Patients JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 96 OP 99 VO 29 IS 2 A1 Amita S. Joshi A1 Henry J. Pieniaszek, Jr. A1 Everett E. Vokes A1 Nicholas J. Vogelzang A1 Anna F. Davidson A1 Lauren E. Richards A1 Min F. Chai A1 Michael Finizio A1 Mark J. Ratain YR 2001 UL http://dmd.aspetjournals.org/content/29/2/96.abstract AB Losoxantrone is an anthrapyrazole derivative in Phase III development in the U.S. for solid tumors, notably breast cancer. To obtain information on the routes of elimination of the drug, a study was conducted in four patients with advanced solid tumors, which involved intravenous administration of 100 μCi of [14C]losoxantrone for a total dose of 50 mg/m2 during the first course of losoxantrone therapy. Blood, urine, and feces were collected for up to 2 weeks and were analyzed for total radioactivity and parent drug. In addition, feces were profiled for the presence of metabolites. Plasma concentrations of total radioactivity exhibited a temporal pattern similar to the parent drug. Combined recovery of administered total radioactivity from urine and feces was 70% with the majority (87%) of this radioactivity excreted in the feces, presumably via biliary excretion. Feces extracts were profiled for metabolites using a high-performance liquid chromatography method developed to separate synthetic standards of previously identified human urinary metabolites. Only intact losoxantrone was found in the feces. About 9% of the dose was excreted in the urine, primarily during the first 24 h and mostly in the form of parent compound. Collectively, these data indicate that fecal excretion of unmetabolized drug via biliary and/or intestinal excretion is the primary pathway of intravenously administered losoxantrone elimination in cancer patients with refractory solid tumors. The American Society for Pharmacology and Experimental Therapeutics