Human hepatic metabolism of the anxiolytic agent, RWJ-51521--API-MS/MS identification of metabolites.
The In vitro metabolism of the anxiolytic agent, RWJ-51521 was conducted after incubation with human hepatic S9 fraction in the presence of an NADPH-generating system. Unchanged RWJ-51521 (30% of the sample) and a total of 11 metabolites were profiled, quantified, and tentatively identified on the basis of API (ionspray)-MS/MS data. The 4 proposed metabolic pathways for RWJ-51521 are: (1) N/O-dealkylation, (2) phenylhydroxylation, (3) pyrido-oxidation, and (4) dehydration. Pathway 1 formed 2 major and 3 minor N/O-desalkyl metabolites (M1 & M3, 50%) and in conjunction with pathway 4, formed 2 moderate dehydrated metabolites (M4 & M5, 14%). Pathways 2 and 3 alone, and in conjunction with pathway 4, produced 4 minor metabolites (each < or =2%). RWJ-51521 is extensively metabolized in human hepatic S9 fraction.
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Johnson & Johnson Pharmaceutical Research & Development, LLC, Spring House, PA 19477, USA.
McKown
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Reitz
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D000577:Amides / Q000378:metabolism*; D014151:Anti-Anxiety Agents / Q000032:analysis / Q000378:metabolism*; D001388:Aziridines; D001562:Benzimidazoles / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D013058:Mass Spectrometry / Q000379:methods; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
C501044:7-fluoro-1,2-dihydro-5-(2-(N-methyl-N-(2-methoxyethyl)amino)ethyl)-3-oxo-N-(2-fluorophenyl)pyrido(1,2-a)benzimidazole-4-carboxamide hydrochloride; D000577:Amides; D014151:Anti-Anxiety Agents; D001388:Aziridines; D001562:Benzimidazoles; C071269:6-N-aziridinyl-3-hydrox-7-methyl-2,3-dihydro-1H-pyrrolo(1,2-a)benzimidazole-5,8-dione 3-acetate
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