Abstract |
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 microCi of [14C] losoxantrone for a total dose of 50 mg/m(2) 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.
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Authors | A S Joshi, H J Pieniaszek Jr, E E Vokes, N J Vogelzang, A F Davidson, L E Richards, M F Chai, M Finizio, M J Ratain |
Journal | Drug metabolism and disposition: the biological fate of chemicals
(Drug Metab Dispos)
Vol. 29
Issue 2
Pg. 96-9
(Feb 2001)
ISSN: 0090-9556 [Print] United States |
PMID | 11159796
(Publication Type: Journal Article)
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Chemical References |
- Anthraquinones
- Antineoplastic Agents
- Carbon Radioisotopes
- Pyrazoles
- Pyrazolones
- losoxantrone
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Topics |
- Anthraquinones
(administration & dosage, blood, pharmacokinetics, urine)
- Antineoplastic Agents
(administration & dosage, blood, pharmacokinetics, urine)
- Carbon Radioisotopes
- Feces
- Humans
- Infusions, Intravenous
- Neoplasms
(blood, drug therapy, metabolism, urine)
- Pyrazoles
(administration & dosage, blood, pharmacokinetics, urine)
- Pyrazolones
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