Table 1. Bupropion Axitinib buy and Bupropion Metabolite Pharmacokinetics in Active Smokers of Nonmenthol and Menthol Cigarettes The first question was whether the Cmax and AUC of bupropion and its metabolites differed between smokers of nonmenthol versus menthol cigarettes. As shown in Table 1, no differences were found between smokers of nonmenthol and menthol cigarettes in these measures. The second question was to determine the effects of smoking abstinence on the PKs of bupropion and its metabolites and to see if this differed between nonmenthol and menthol cigarette smokers. Forty-three percent (10/23, 9 cotinine verified) menthol smokers and 29% (5/17, 4 cotinine verified) nonmenthol smokers reported 7-day abstinence from smoking at end of nonsmoking condition.

Of this number, only three nonmenthol and four menthol participants had evaluable plasma samples. Due to the small number of abstinent participants with evaluable data, analysis of the nonsmoking condition was conducted for exploratory purposes to inform future studies. There were no differences between menthol and nonmenthol smokers in the AUC of bupropion or its metabolites in the nonsmoking condition. However, among menthol smokers, the AUC ratios of metabolite/bupropion were lower in the nonsmoking compared with the smoking condition (hydro/bup = 31.49 �� 18.84 vs. 22.95 �� 13.27, p = .04; erythro/bup = 1.99 �� 1.02 vs. 1.76 �� 0.75, p = .016; threo/bup = 11.77 �� 8.90 vs. 10.44 �� 5.63, p = .034). The differences in ratios between the two conditions ranged 13%�C17%.

No significant differences were found in the metabolite/bup ratios between smoking and nonsmoking conditions among nonmenthol smokers. Discussion The aim of our study was to determine if smoking menthol cigarettes affects the metabolism and PKs of bupropion and its metabolites in a way that could explain lower rates of smoking cessation with bupropion treatment of menthol cigarette smokers compared with nonmenthol cigarette smokers. A comparison of menthol versus nonmenthol cigarette smokers demonstrated no difference in bupropion or metabolite levels in steady-state conditions of dosing, suggesting that the menthol does not alter bupropion PKs. While we did not find group differences between menthol and nonmenthol cigarette smokers, we did observe in a subgroup analysis that among menthol cigarette smokers, stopping smoking was associated with a small statistically significant increase in bupropion concentrations.

This finding suggests that among menthol smokers, smoking may induce bupropion metabolism to a small extent such that bupropion levels rise after stopping smoking. However, the magnitude of the change ranged 13%�C17%, which is not likely to Brefeldin_A be pharmacologically significant. The enzymes and mechanisms by which menthol might produce such an effect are unknown and require further study.