Metabolism of Nicotine and 4-(methylnitrosamino)-l-(3-pyridyl)-lbutanone (NNK) in Menthol and Non-menthol Cigarette Smokers

Abstract

Menthol in cigarettes has been suggested to inhibit metabolism of nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The objective of this study was to investigate the glucuronide metabolite ratios (MR) for nicotine (NICGLUC/NIC), cotinine (COTGLUC/COT), trans 3'-hydroxy cotinine (3OHCOTGLUC/3OHCOT). 4-methylnitrosamino-1-(3-pyridyl)-1-butanol (NNAL - NNALGLUC/NNAL); and the ratio of trans 3'-hydroxy cotinine tocotinine (3OHCOT/COT) between adult menthol and non-menthol smokers (AS). The data was collected from the Total Exposure Study (TES), a stratified, multi-center, cross-sectional study that included 3,585 AS and 1,077 non-smokers. Daily urinary excretion of nicotine and five metabolites, NNAL and NNAL glucuronides, and serum cotinine were measured in the AS. The analysis included 1044 menthol (448 African-Americans, AA) and 2297 non-menthol (161 AA) AS. Smoking mentholated cigarettes did not decrease any of the MR. Race was the most important significant main effect for all the MRs. AAs exhibited statistically significantly lower NICGLUC/NIC, COTGLUC/COT, NNALGLUC/NNAL and 3OHCOT/COT, but higher 3OHCOTGLUC/3OHCOT compared to Whites. Age, liver function, alcoholic beverages, etc., were some of the other significant effects for some MRs. Menthol was not a statistically significant effect,e.g. the adjusted mean NNALGLUC/NNAL between menthol and non-menthol AS was 2.93 vs. 2.80 (p>0.05, AA) and3.38 vs. 3.35 (p>0.05, Whites). The models only explained 2.6-12.6% of the MR variability. Number of cigarettes was the most important factor affecting serum cotinine levels. Menthol does not inhibit the metabolism of nicotine or NNK. The daily exposure of related constituents is primarily influenced by number of cigarettes smoked per day.