title: The Nicotine Metabolite Ratio is Associated With Early Smoking Abstinence Even After Controlling for Factors That Influence the Nicotine Metabolite Ratio.
abstract: BACKGROUND
  The decrease in smoking rates in North America has plateaued, underscoring the need for new approaches to treat nicotine dependence. Inter-individual differences in smoking behavior result, in part, from variation in the rate of CYP2A6-mediated nicotine metabolism. A phenotypic measure of CYP2A6 activity is the nicotine metabolite ratio (NMR), the ratio of 3'hydroxycotinine/cotinine. The NMR is associated with smoking cessation. However, the NMR is also associated with genetic (eg, CYP2A6 genotype) and other (eg, sex and ethnicity) factors. Here we aimed to determine if previously identified non-CYP2A6 sources of variation in the NMR mitigated the association between the NMR and short-term abstinence.
  
  
  METHODS
  The NMR was determined from blood samples collected at intake from daily smokers aged 18-65. Biochemically-verified point prevalence abstinence (exhaled carbon monoxide level ≤ 8 ppm) was measured at 1 week following the target quit date in participants from a smoking cessation clinical trial (NCT01314001). Analyses were restricted to N = 462 blacks and N = 693 whites in the intent-to-treat sample.
  
  
  RESULTS
  Lower NMR (<0.31) was associated with a higher likelihood of 1-week abstinence (OR = 1.43; 95% CI = 1.12, 1.84). NMR was associated with abstinence even after controlling for treatment arm (nicotine patch or varenicline) and factors previously associated with NMR variation including sex, ethnicity, estrogen-containing hormonal therapy, body mass index, alcohol, and cigarette consumption.
  
  
  CONCLUSIONS
  NMR was associated with 1-week smoking abstinence; NMR may be a useful addition to medication screening approaches evaluating treatments for nicotine dependence.
authors.affiliation: Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada;
authors.forename: Meghan J
authors.initials: MJ
authors.lastname: Chenoweth
authors.affiliation: Center for Interdisciplinary Research on Nicotine Addiction, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA;
authors.forename: Robert A
authors.initials: RA
authors.lastname: Schnoll
authors.affiliation: Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada;
authors.forename: Maria
authors.initials: M
authors.lastname: Novalen
authors.affiliation: Department of Psychology and Center for Children and Families, University at Buffalo, SUNY, Buffalo, NY;
authors.forename: Larry W
authors.initials: LW
authors.lastname: Hawk
authors.affiliation: Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada;
authors.forename: Tony P
authors.initials: TP
authors.lastname: George
authors.affiliation: Department of Behavioral Science, University of Texas MD Anderson Cancer Center, Houston, TX;
authors.forename: Paul M
authors.initials: PM
authors.lastname: Cinciripini
authors.affiliation: Center for Interdisciplinary Research on Nicotine Addiction, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA;
authors.forename: Caryn
authors.initials: C
authors.lastname: Lerman
authors.affiliation: Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada r.tyndale@utoronto.ca.
authors.forename: Rachel F
authors.initials: RF
authors.lastname: Tyndale
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage / Q000378:metabolism*; D011446:Prospective Studies; D012907:Smoking / Q000378:metabolism* / Q000628:therapy; D016540:Smoking Cessation / Q000379:methods; D013997:Time Factors; D061485:Tobacco Use Cessation Devices; D014029:Tobacco Use Disorder / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D000068580:Varenicline / Q000627:therapeutic use
chemical_list: D009538:Nicotine; D000068580:Varenicline