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Rates of excretion of cotinine, nicotine glucuronide, and 3- hydroxycotinine glucuronide in rat bile

MJ Seaton, GA Kyerematen and ES Vesell

Department of Pharmacology, Pennsylvania State University, College of Medicine, Hershey 17033.

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.

Volume 21, Issue 5, pp. 927-932, 09/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1993 by the American Society for Pharmacology and Experimental Therapeutics.