title: Metabolism of (-)-(S)-nicotine in the isolated perfused rabbit lung.
abstract: The metabolism of (-)-(S)-nicotine has been investigated following intratracheal administration to the recirculating perfused rabbit lung model. The metabolic products present in the perfusate were identified by co-chromatography (HPLC and GC) with authentic standards and quantified by HPLC. After the 180 min perfusion period, nicotine was found to be metabolically transformed to cotinine (33.7%), 3-hydroxycotinine (10.4%), cotinine-1-N-oxide (3.4%) and nicotine-1'-N-oxide (14.4%). Norcotinine, nornicotine, 3-pyridyl-4-oxo-N-methylbutyramide and an uncharacterised metabolite were also detected in low amounts. Following the perfusion experiment, part of the lung tissue was homogenised in the presence of [14C]-sodium cyanide. Subsequent analysis of the homogenates indicated the formation of 2'-cyanonicotine, 1'-cyanomethylnornicotine and the diastereoisomeric 5'-cyanonicotines.
authors.affiliation: Chelsea Department of Pharmacy, King's College London, University of London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Aislaitner
authors.forename: A
authors.initials: A
authors.lastname: Bello
authors.forename: S C
authors.initials: SC
authors.lastname: Tan
authors.forename: A J
authors.initials: AJ
authors.lastname: Hutt
authors.forename: C
authors.initials: C
authors.lastname: Marriott
authors.forename: J W
authors.initials: JW
authors.lastname: Gorrod
mesh_terms: D000818:Animals; D001711:Biotransformation; D002138:Calibration; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D003486:Cyanides; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D009538:Nicotine / Q000493:pharmacokinetics*; D018722:Nicotinic Agonists / Q000493:pharmacokinetics*; D011817:Rabbits; D013237:Stereoisomerism
chemical_list: D003486:Cyanides; D018722:Nicotinic Agonists; D009538:Nicotine