RATES OF EXCRETION OF COTININE, NICOTINE GLUCURONIDE, AND 3-HYDROXYCOTININE GLUCURONIDE IN RAT BILE

A new HPLC assay was adapted for radiometric detection of nicotine met abolites in rat bile. Two glucuronides were identified as the principa l 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-n icotine (0.2 or 1.0 mg/kg) that contained a tracer dose of rac-[pyrrol idine-2'-C-14]nicotine (20 muCi). Biliary metabolites accounted for on ly 3% of the [C-14]nicotine dose, but phenobarbital pretreatment (100 mg/kg ip for 3 days) increased the amount of [C-14] nicotine-derived r adioactivity recovered in bile to 8% and also accelerated rates of bil iary excretion of all three nicotine metabolites. Dose-dependency of n icotine metabolism occurred: less nicotine glucuronide was excreted at the low dose than at the high dose.