title: Characterization of the metabolites of alosetron in experimental animals and human.
abstract: 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.
authors: DMPK, GlaxoSmithKline Research and Development, Ware, UK. i.m.ismail@blueyonder.co.uk
authors: I M
authors: IM
authors: Ismail
authors: P D
authors: PD
authors: Andrew
authors: J
authors: J
authors: Cholerton
authors: A D
authors: AD
authors: Roberts
authors: G J
authors: GJ
authors: Dear
authors: S
authors: S
authors: Taylor
authors: K M
authors: KM
authors: Koch
authors: D A
authors: DA
authors: Saynor
mesh_terms: D000818:Animals; D002243:Carbolines / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D004285:Dogs; D005260:Female; D005765:Gastrointestinal Agents / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008956:Models, Chemical; D011817:Rabbits; D011854:Radiochemistry / Q000379:methods; D051381:Rats; D012702:Serotonin Antagonists / Q000737:chemistry; D013045:Species Specificity; D013997:Time Factors
chemical_list: D002243:Carbolines; D005765:Gastrointestinal Agents; D012702:Serotonin Antagonists; C090840:alosetron