Species Variation in the Metabolism of R-(+)- and S-(-)-Nicotine by α-C- andN-Oxidationin vitro

Abstract
1. Marked species, but not sex differences, were observed in the metabolism of R-(+)- and S-(-)-nicotine to cotinine and the diastereoisomeric nicotine-1′-N-oxides by liver 10 000 × g supernatant preparations from rats, rabbits, mice, guinea-pigs and hamsters. 2. S-(-)-nicotine formed predominantly R,S-cis-nicotine-1′-N-oxide, whereas R-(+)-nicotine gave predominantly S,R-trans-nicotine-1′-N-oxide; stereoselective metabolism to cotinine also occurred. A stereo-selective site for the N-oxidation of nicotine is proposed to explain these results.