Metabolism of pentyl 2-chloro-4-fluoro-5-(3,4,5,6-tetrahydrophthalimido)phenoxyacetate (flumiclorac pentyl, S-23031) in rats. 2. Absorption, distribution, biotransformation, and excretion.

摘要

Male and female Sprague-Dawley rats, 7 weeks old, were given a single oral dose of [phenyl-14C]-flumiclorac (PH-FC) or [tetrahydrophthaloyl-1,2-14C]-flumiclorac (THP-FC) at 1 or 500 mg/kg. 14C was rapidly excreted into faeces and urine, and more than 90% of the 14C administered was recovered within 48 h post-treatment. 14C levels in tissues and blood were generally low on the seventh day after dosing. However, rats treated with THP-FC exhibited relatively higher levels than those treated with PH-FC.Flumiclorac was rapidly and extensively metabolized. Major faecal metabolites were the sulfonic acid conjugates, and the major urinary metabolite was 5-amino-2-chloro-4-fluorophenoxyacetic acid. The main metabolic reactions were: cleavage of the ester linkage; cleavage of the imide linkage: 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 incorporation of a sulfonic acid group into the >C=C< double bond of the 3,4,5,6-tetrahydrophthalimide moiety.