The pharmacokinetics and pharmacodynamics of nicotine, after single and repetitive doses, will be examined in healthy volunteers and patients with coronary heart disease; and as a function of urinary pH and of age. Diurnal variation in nicotine blood concentrations, heart rate and rhythm, electro-cardiographic (Q-T) intervals and urinary catecholamine excretion during daily smoking of medium and low nicotine cigarettes will be studied. The relationship between nicotine blood concentrations and cardiovascular effects and aversiveness of the experience during rapid smoking of low, medium and high nicotine tobacco cigarettes will be examined. Pharmacokinetic data will be used to predict the time course of nicotine in the body during habitual tobacco smoking and to design future experiments to further explore the role of nicotine in tobacco dependence. Pharmacologic response data will be used in combination with kinetic data to predict periods of maximal effect and high risk periods for adverse cardiovascular effects.

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National Institute on Drug Abuse (NIDA)
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University of California San Francisco
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Taghavi, Taraneh; St Helen, Gideon; Benowitz, Neal L et al. (2017) Effect of UGT2B10, UGT2B17, FMO3, and OCT2 genetic variation on nicotine and cotinine pharmacokinetics and smoking in African Americans. Pharmacogenet Genomics 27:143-154
Ross, Kathryn C; Dempsey, Delia A; St Helen, Gideon et al. (2016) The Influence of Puff Characteristics, Nicotine Dependence, and Rate of Nicotine Metabolism on Daily Nicotine Exposure in African American Smokers. Cancer Epidemiol Biomarkers Prev 25:936-43
Gubner, Noah R; Kozar-Konieczna, Aleksandra; Szoltysek-Boldys, Izabela et al. (2016) Cessation of alcohol consumption decreases rate of nicotine metabolism in male alcohol-dependent smokers. Drug Alcohol Depend 163:157-64
Benowitz, Neal L; St Helen, Gideon; Dempsey, Delia A et al. (2016) Disposition kinetics and metabolism of nicotine and cotinine in African American smokers: impact of CYP2A6 genetic variation and enzymatic activity. Pharmacogenet Genomics 26:340-50
Baurley, James W; Edlund, Christopher K; Pardamean, Carissa I et al. (2016) Genome-Wide Association of the Laboratory-Based Nicotine Metabolite Ratio in Three Ancestries. Nicotine Tob Res 18:1837-1844
Benowitz, Neal L; Nardone, Natalie; Dains, Katherine M et al. (2015) Effect of reducing the nicotine content of cigarettes on cigarette smoking behavior and tobacco smoke toxicant exposure: 2-year follow up. Addiction 110:1667-75
Wassenaar, Catherine A; Conti, David V; Das, Soma et al. (2015) UGT1A and UGT2B genetic variation alters nicotine and nitrosamine glucuronidation in european and african american smokers. Cancer Epidemiol Biomarkers Prev 24:94-104
Shiffman, Saul; Dunbar, Michael S; Benowitz, Neal L (2014) A comparison of nicotine biomarkers and smoking patterns in daily and nondaily smokers. Cancer Epidemiol Biomarkers Prev 23:1264-72
Hajek, Peter; Etter, Jean-Fran├žois; Benowitz, Neal et al. (2014) Electronic cigarettes: review of use, content, safety, effects on smokers and potential for harm and benefit. Addiction 109:1801-10
Leventhal, Adam M; Lee, Wonho; Bergen, Andrew W et al. (2014) Nicotine dependence as a moderator of genetic influences on smoking cessation treatment outcome. Drug Alcohol Depend 138:109-17

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