Metabolic disposition and irreversible binding of 1-phenylcyclohexene in rats.

The metabolic disposition of 1-[14C]phenylcyclohexene ([14C]PC) was examined in rats after ip or iv drug administration. Radioactivity, which was accumulated by various organs, peaked within 30 min after ip administration of [14C]PC (0.21 mg/kg). A significant amount of this radioactivity was not extractable by repeated methanol extractions, indicating irreversible binding of [14C]PC metabolite(s) to tissue proteins. Following iv administration of [14C]PC (0.42 mg/kg), [14C]PC concentrations in blood declined biphasically with time; the blood elimination half-life of [14C]PC is 77 min. About 83% of the dose given was excreted in urine and feces within 54 hr of administration. About 35% of the dose was excreted in the bile in 1 hr. At least four [14C]PC metabolites were detected in the urine or bile. The bulk of the urinary radioactivity was composed of metabolites since less than 6% of [14C]PC given was excreted unchanged in the urine.