METABOLISM OF (-)-(S)-NICOTINE IN THE ISOLATED-PERFUSED RABBIT LUNG

The metabolism of (-)-(S)-nicotine has been investigated following int ratracheal administration to the recirculating perfused rabbit lung mo del. The metabolic products present in the perfusate were identified b y co-chromatography (HPLC and GC) with authentic standards and quantif ied 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%). Nor cotinine, nornicotine, 3-pyridyl-4-oxo-N-methylbutyramide and an uncha racterised metabolite were also detected in low amounts. Following the perfusion experiment, part of the lung tissue was homogenised in the presence of [C-14]-sodium cyanide. Subsequent analysis of the homogena tes indicated the formation of 2'-cyanonicotine, 1'-cyanomethylnornico tine and the diastereoisomeric 5'-cyanonicotines.