Characterization of the metabolites of alosetron in experimental animals and human

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 metabolit...

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Bibliographic Details
Published in:Xenobiotica 2005-02, Vol.35 (2), p.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: Article
Language:English
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
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Summary: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.
ISSN:0049-8254
1366-5928
DOI:10.1080/00498250400028247