Characterization of the metabolites of alosetron in experimental animals and human

• Published in: Xenobiotica Vol. 35; no. 2; pp. 131 - 154
• Main Authors: Ismail, I. M, Andrew, P. D, Cholerton, J, Roberts, A. D, Dear, G. J, Taylor, S, Koch, K. M, Saynor, D. A
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01-02-2005; Taylor & Francis
• Subjects: 5-HT3 antagonists; Alosetron; Animals; Carbolines - chemistry; Carbolines - metabolism; Carbolines - pharmacokinetics; Chromatography, High Pressure Liquid; Chromatography, Liquid; Dogs; Female; Gastrointestinal Agents - chemistry; Gastrointestinal Agents - metabolism; Gastrointestinal Agents - pharmacokinetics; Humans; irritable bowel syndrome (IBS); Irritable Bowel Syndrome - drug therapy; Magnetic Resonance Spectroscopy; Male; Mass Spectrometry; metabolism; Mice; Models, Chemical; Rabbits; Radiochemistry - methods; Rats; Serotonin Antagonists - chemistry; Species Specificity; Time Factors
• ISSN: 0049-8254; 1366-5928
• DOI: 10.1080/00498250400028247

The metabolism of radiolabelled alosetron was studied in rat, dog, rabbit, mouse and human. The metabolism in rat and dog was studied at a low and an elevated dose designed to generate sufficient quantities of metabolite for definitive identification. A strategy for the characterization of metabolites in cases of extensive metabolism was developed and demonstrated for alosetron. Semi-preparative high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), nuclear magnetic resonance (NMR) and liquid chromatography-nuclear magnetic resonance (HPLC-NMR) enabled the isolation and characterization of 28 metabolites of alosetron. The characterization of the metabolites in animal excreta facilitated the identification of human systemic metabolites.