title: Racial differences in the relationship between rate of nicotine metabolism and nicotine intake from cigarette smoking.
abstract: Rate of nicotine metabolism has been identified as an important factor influencing nicotine intake and can be estimated using the nicotine metabolite ratio (NMR), a validated biomarker of CYP2A6 enzyme activity. Individuals who metabolize nicotine faster (higher NMR) may alter their smoking behavior to titrate their nicotine intake in order to maintain similar levels of nicotine in the body compared to slower nicotine metabolizers. There are known racial differences in the rate of nicotine metabolism with African Americans on average having a slower rate of nicotine metabolism compared to Whites. The goal of this study was to determine if there are racial differences in the relationship between rate of nicotine metabolism and measures of nicotine intake assessed using multiple biomarkers of nicotine and tobacco smoke exposure. Using secondary analyses of the screening data collected in a recently completed clinical trial, treatment-seeking African American and White daily smokers (10 or more cigarettes per day) were grouped into NMR quartiles so that the races could be compared at the same NMR, even though the distribution of NMR within race differed. The results indicated that rate of nicotine metabolism was a more important factor influencing nicotine intake in White smokers. Specifically, Whites were more likely to titrate their nicotine intake based on the rate at which they metabolize nicotine. However, this relationship was not found in African Americans. Overall there was a greater step-down, linear type relationship between NMR groups and cotinine or cotinine/cigarette in African Americans, which is consistent with the idea that differences in blood cotinine levels between the African American NMR groups were primarily due to differences in CYP2A6 enzyme activity without titration of nicotine intake among faster nicotine metabolizers.
authors.affiliation: Center for Tobacco Control Research and Education, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Kathryn C
authors.initials: KC
authors.lastname: Ross
authors.affiliation: Center for Tobacco Control Research and Education, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Noah R
authors.initials: NR
authors.lastname: Gubner
authors.affiliation: Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Rachel F
authors.initials: RF
authors.lastname: Tyndale
authors.affiliation: Department of Psychology University at Buffalo, SUNY, Buffalo, NY, USA.
authors.forename: Larry W
authors.initials: LW
authors.lastname: Hawk
authors.affiliation: Department of Psychiatry and Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Annenberg School for Communication, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Caryn
authors.initials: C
authors.lastname: Lerman
authors.affiliation: Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Tony P
authors.initials: TP
authors.lastname: George
authors.affiliation: Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Cinciripini
authors.affiliation: Department of Psychiatry and Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Schnoll
authors.affiliation: Center for Tobacco Control Research and Education, University of California San Francisco, San Francisco, CA, USA; Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, University of California San Francisco, San Francisco, CA, USA; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA. Electronic address: neal.benowitz@ucsf.edu.
authors.forename: Neal L
authors.initials: NL
authors.lastname: Benowitz
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D002248:Carbon Monoxide / Q000378:metabolism; D003367:Cotinine / Q000097:blood; D065637:Cytochrome P-450 CYP2A6 / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage / Q000378:metabolism*; D012907:Smoking; D062789:Tobacco Products; D044465:White People
chemical_list: D009538:Nicotine; D002248:Carbon Monoxide; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; D003367:Cotinine
keywords: African American smokers; Biomarkers; Nicotine intake; Nicotine metabolism; Nicotine titration; Racial differences