Metabolism of Nicotine by the Isolated Perfused Dog Lung

Abstract

1. Metabolism of [¹⁴C]nicotine has been studied in the isolated perfused dog lung. [¹⁴C]Nicotine, 50 μg every 30 s for 10 min administered via the pulmonary artery, undergoes first pass metabolism to a small extent. [¹⁴C]Cotinine was detected in the venous blood. Of the injected activity, 6% was in the lung at the end of experiment; 60% being present as [¹⁴C]nicotine and 20% as [¹⁴C]nicotine-1′-oxide.

2. When [¹⁴C]nicotine was administered in cigarette smoke a greater degree of metabolism was observed at first pass. Pyrolysis products of [¹⁴C]nicotine also were present in the venous blood. Lungs after smoke exposure contained 30% of administered radioactivity, with a substantial proportion of [¹⁴C]-nicotine-1′-oxide.

3. Administration of [¹⁴C]nicotine-labelled smoke to lung preparations, on closed circuit, gave significant amounts of [¹⁴C]cotinine and other metabolites over a 2 h period. Lung tissue contained approx. 40% of injected dose, of which 25% only was [¹⁴C]nicotine. Large proportions of [¹⁴C]cotinine and [¹⁴C]-nicotine-1′-oxide were present but 45% of the activity was present as other unidentified pyrolysis products. [¹⁴C]Demethyl cotinine was detected.