Factors Affecting the in vitro Metabolism of R-(+)-and S-(-)-Nicotine by Guinea-pig Liver Preparations

Abstract

1. Cotinine and the diastereoisomeric nicotine-1-N-oxides were the major in vitro metabolites of R-(+)- and S-(-)-nicotine produced by various guineapig hepatic preparations; metabolism was greatest in the 10 000 × g supernatant fraction, being enzymic and NADP(H) dependent. The effect of various substrate concentrations and incubation times on metabolism in the 10 000 × g supernatant fraction was investigated.

2. The ratio of the diastereoisomeric N-oxides formed was markedly stereoselective but the formation of cotinine and disappearance of nicotine were not.

3. Cotinine formation, but not the disappearance of nicotine or formation of nicotine-1′-N-oxide, was inhibited by SKF 525A and KCN.