BACKGROUND:Nicotine is metabolized to cotinine, and cotinine is metabolized to 3'-hydroxycotinine (3-HC) by the liver enzyme cytochrome P450 (CYP) 2A6. More rapid metabolism of nicotine may result in lower nicotine blood levels from nicotine replacement products and poorer smoking cessation outcomes. This study evaluated the utility of the 3-HC/cotinine ratio as a predictor of the efficacy of nicotine replacement therapy as an aid for smoking cessation. METHODS: By use of an open-label design, 480 treatment-seeking smokers were randomly assigned to 8 weeks of transdermal nicotine or nicotine nasal spray use, plus behavioral group counseling. Assessments included demographics, smoking history, body mass index, and plasma nicotine, cotinine, and 3-HC concentrations, as well as CYP2A6 genotypes. Smoking cessation was biochemically verified at the end of treatment and at 6-month follow-up. RESULTS: The rate of nicotine metabolism, as indicated by pretreatment 3-HC/cotinine ratio derived from cigarette smoking, predicted the effectiveness of transdermal nicotine at both time points. The odds of abstinence were reduced by almost 30% with each increasing quartile of metabolite ratio (odds ratio, 0.72 [95% confidence interval, 0.57-0.90]; P=.005). Higher metabolite ratios also predicted lower nicotine concentrations (beta=-1.72, t(179)=-3.31, P<.001), as well as more severe cravings for cigarettes after 1 week of treatment (beta=0.32, t(190)=2.91, P=.004). The metabolite ratio did not predict cessation with use of nicotine nasal spray (odds ratio, 1.05 [95% confidence interval, 0.83-1.33]; P=.68). CONCLUSION: The nicotine metabolite ratio might be useful in screening smokers to determine likely success with a standard dose of transdermal nicotine.
RCT Entities:
BACKGROUND:Nicotine is metabolized to cotinine, and cotinine is metabolized to 3'-hydroxycotinine (3-HC) by the liver enzyme cytochrome P450 (CYP) 2A6. More rapid metabolism of nicotine may result in lower nicotine blood levels from nicotine replacement products and poorer smoking cessation outcomes. This study evaluated the utility of the 3-HC/cotinine ratio as a predictor of the efficacy of nicotine replacement therapy as an aid for smoking cessation. METHODS: By use of an open-label design, 480 treatment-seeking smokers were randomly assigned to 8 weeks of transdermal nicotine or nicotine nasal spray use, plus behavioral group counseling. Assessments included demographics, smoking history, body mass index, and plasma nicotine, cotinine, and 3-HC concentrations, as well as CYP2A6 genotypes. Smoking cessation was biochemically verified at the end of treatment and at 6-month follow-up. RESULTS: The rate of nicotine metabolism, as indicated by pretreatment 3-HC/cotinine ratio derived from cigarette smoking, predicted the effectiveness of transdermal nicotine at both time points. The odds of abstinence were reduced by almost 30% with each increasing quartile of metabolite ratio (odds ratio, 0.72 [95% confidence interval, 0.57-0.90]; P=.005). Higher metabolite ratios also predicted lower nicotine concentrations (beta=-1.72, t(179)=-3.31, P<.001), as well as more severe cravings for cigarettes after 1 week of treatment (beta=0.32, t(190)=2.91, P=.004). The metabolite ratio did not predict cessation with use of nicotine nasal spray (odds ratio, 1.05 [95% confidence interval, 0.83-1.33]; P=.68). CONCLUSION: The nicotine metabolite ratio might be useful in screening smokers to determine likely success with a standard dose of transdermal nicotine.
Authors: Jacob G Dubroff; Robert K Doot; Mary Falcone; Robert A Schnoll; Riju Ray; Rachel F Tyndale; Arthur L Brody; Catherine Hou; Alexander Schmitz; Caryn Lerman Journal: J Nucl Med Date: 2015-08-13 Impact factor: 10.057
Authors: C Lerman; C Jepson; E P Wileyto; F Patterson; R Schnoll; M Mroziewicz; N Benowitz; R F Tyndale Journal: Clin Pharmacol Ther Date: 2010-03-24 Impact factor: 6.875
Authors: K M Giacomini; C M Brett; R B Altman; N L Benowitz; M E Dolan; D A Flockhart; J A Johnson; D F Hayes; T Klein; R M Krauss; D L Kroetz; H L McLeod; A T Nguyen; M J Ratain; M V Relling; V Reus; D M Roden; C A Schaefer; A R Shuldiner; T Skaar; K Tantisira; R F Tyndale; L Wang; R M Weinshilboum; S T Weiss; I Zineh Journal: Clin Pharmacol Ther Date: 2007-03 Impact factor: 6.875
Authors: K J Bough; C Lerman; J E Rose; F J McClernon; P J Kenny; R F Tyndale; S P David; E A Stein; G R Uhl; D V Conti; C Green; S Amur Journal: Clin Pharmacol Ther Date: 2013-03-18 Impact factor: 6.875
Authors: Andrew W Bergen; Harold S Javitz; Ruth Krasnow; Denise Nishita; Martha Michel; David V Conti; Jinghua Liu; Won Lee; Christopher K Edlund; Sharon Hall; Pui-Yan Kwok; Neal L Benowitz; Timothy B Baker; Rachel F Tyndale; Caryn Lerman; Gary E Swan Journal: Pharmacogenet Genomics Date: 2013-02 Impact factor: 2.089