title: Nicotine metabolic rate predicts successful smoking cessation with transdermal nicotine: a validation study.
abstract: Transdermal nicotine is widely used for smoking cessation, but only approximately 20% of smokers quit successfully with this medication. Interindividual variability in nicotine metabolism rate may influence treatment response. This study sought to validate, and extend in a larger sample, our previous finding that the ratio of plasma nicotine metabolites 3'-hydroxycotinine (3-HC)/cotinine, a measure of nicotine metabolism rate, predicts response to nicotine patch. A sample of 568 smokers was enrolled in a study that provided counseling and 8-weeks of 21 mg nicotine patch. Pretreatment 3-HC/cotinine ratio was examined as a predictor of 7-day point prevalence abstinence, verified with breath carbon monoxide (CO), 8 weeks after the quit date. Controlling for sex, race, age, and nicotine dependence, smokers in the upper 3 quartiles of 3-HC/cotinine ratio (faster metabolizers) were approximately 50% less likely to be abstinent vs. smokers in the first quartile (slow metabolizers; 28% vs. 42%; OR=.54 [95% CI:.36-.82], p=.003). Among abstainers, plasma nicotine levels (assessed 1 week after treatment began) decreased linearly across the 3-HC/cotinine ratio (beta=-3.38, t[355]=-3.09, p<.05). These data support the value of the 3-HC/cotinine ratio as a biomarker to predict success with transdermal nicotine for smoking cessation.
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA. schnoll@mail.med.upenn.edu
authors.forename: Robert A
authors.initials: RA
authors.lastname: Schnoll
authors.forename: Freda
authors.initials: F
authors.lastname: Patterson
authors.forename: E Paul
authors.initials: EP
authors.lastname: Wileyto
authors.forename: Rachel F
authors.initials: RF
authors.lastname: Tyndale
authors.forename: Neal
authors.initials: N
authors.lastname: Benowitz
authors.forename: Caryn
authors.initials: C
authors.lastname: Lerman
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers; D003367:Cotinine / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D012372:ROC Curve; D016540:Smoking Cessation / Q000706:statistics & numerical data*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D018722:Nicotinic Agonists; D009538:Nicotine; D003367:Cotinine