Wn. Wu et al., IN-VITRO AND IN-VIVO METABOLISM OF THE ANTIANXIOLYTIC AGENT FENOBAM IN THE RAT, Journal of pharmaceutical sciences, 84(2), 1995, pp. 185-189
Fenobam [(Fn); N-(3-chlorophenyl)-N'-(4,5-dihytiro-1-methyl- 4-oxo-1H-
imidazole-2-yl)urea] sulfate is a novel agent with potent anxiolytic a
ctivity in rats. [C-14]Fn sulfate was administered as an oral solution
(250 mg/kg) to male Wistar rats, and 52% of the administered dose was
excreted in urine (0-5 days). In vitro metabolism of Fn was studied b
y incubating [C-14]Fn with rat hepatic 9000 x g supernatant preparatio
ns. Unchanged Fn and a total of six metabolites were isolated, quantif
ied, and identified from the urine and liver 9000 x g supernatant samp
les by column chromatography; TLC; UV, IR, and NMR spectroscopy; MS; a
nd comparison with synthetic samples. Four metabolic pathways for Fn a
re proposed: (1) hydroxylation at the phenyl ring to form 4-hydroxyphe
nyl-Fn, a major pathway in vivo (12% of the sample radioactivity) but
a minor pathway in vitro (4% of the sample radioactivity); (2) hydroxy
lation at the creatinine ring to form 5-hydroxy-Fn (19%) of the sample
radioactivity), a dominant pathway in vitro but not in vivo; (3) oxid
ative cleavage at the creatinine ring (loss of a ketene unit), a minor
pathway for Fn but an important pathway for 4-hydroxyphenyl-Fn in viv
o; and (4) N-demethylation, a minor pathway for Fn in vivo.