Human hepatic metabolism of the anxiolytic agent, RWJ-51521--API-MS/MS identification of metabolites.
Eur J Drug Metab Pharmacokinet
; 29(4): 257-62, 2004.
Article
in En
| MEDLINE
| ID: mdl-15726887
ABSTRACT
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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Database:
MEDLINE
Main subject:
Anti-Anxiety Agents
/
Benzimidazoles
/
Spectrometry, Mass, Electrospray Ionization
/
Amides
/
Liver
Type of study:
Diagnostic_studies
Limits:
Humans
Language:
En
Year:
2004
Type:
Article