Metabolism of (-)-(S)-nicotine in the isolated perfused rabbit lung.
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.
Aislaitner
G
G
Chelsea Department of Pharmacy, King's College London, University of London, UK.
Bello
A
A
Tan
S C
SC
Hutt
A J
AJ
Marriott
C
C
Gorrod
J W
JW
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
D003486:Cyanides; D018722:Nicotinic Agonists; D009538:Nicotine