Abstract
Male and female Sprague-Dawley rats, 7 weeks old, were given a single oral dose of [phenyl- 14 C]-S-23031 [pentyl 2-chloro-4-fluoro-5-(3,4,5,6-tetrahydrophthalimido)phenoxyacetate] or [tetrahydrophthaloyl-1,2- 14 C]-S-23031 ([THP- 14 C]-S-23031) at 1 or 500 mg/kg. 14 C was rapidly excreted into feces and urine, and more than 90% of the dosed 14 C was recovered within 48 h post-treatment. 14 C levels in tissues and blood were generally low on the seventh day after dosing. However, those with [THP- 14 C]-S-23031 were relatively higher than those with [phenyl- 14 C]-S-23031. S-23031 was rapidly and extensively metabolized. Major fecal metabolites were the sulfonic acid conjugates, and the major urinary metabolite was 5-amino-2-chloro-4-fluorophenoxyacetic acid. The main metabolic reactions were (1) cleavage of the ester linkage, (2) cleavage of the imide linkage, (3) hydroxylation at the cyclohexene ring of the 3,4,5,6-tetrahydrophthalimide moiety or the cyclohexane ring of the cyclohexane-1,2-dicarboxylic acid moiety, and (4) incorporation of a sulfonic acid group into the >C=C< double bond of the 3,4,5,6-tetrahydrophthalimide moiety.
Published Version
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