PT - JOURNAL ARTICLE AU - M J Seaton AU - G A Kyerematen AU - E S Vesell TI - Rates of excretion of cotinine, nicotine glucuronide, and 3-hydroxycotinine glucuronide in rat bile. DP - 1993 Sep 01 TA - Drug Metabolism and Disposition PG - 927--932 VI - 21 IP - 5 4099 - http://dmd.aspetjournals.org/content/21/5/927.short 4100 - http://dmd.aspetjournals.org/content/21/5/927.full SO - Drug Metab Dispos1993 Sep 01; 21 AB - A new HPLC assay was adapted for radiometric detection of nicotine metabolites in rat bile. Two glucuronides were identified as the principal biliary metabolites of nicotine. In addition to nicotine glucuronide and 3-hydroxycotinine glucuronide, cotinine was also detected in bile after administration to rats of a single subcutaneous dose of (-)-S-nicotine (0.2 or 1.0 mg/kg) that contained a tracer dose of rac-[pyrrolidine-2'-14C]nicotine (20 microCi). Biliary metabolites accounted for only 3% of the [14C]nicotine dose, but phenobarbital pretreatment (100 mg/kg ip for 3 days) increased the amount of [14C]nicotine-derived radioactivity recovered in bile to 8% and also accelerated rates of biliary excretion of all three nicotine metabolites. Dose-dependency of nicotine metabolism occurred: less nicotine glucuronide was excreted at the low dose than at the high dose.