Nicotine metabolic rate predicts successful smoking cessation with transdermal nicotine: a validation study

Pharmacol Biochem Behav. 2009 Mar;92(1):6-11. doi: 10.1016/j.pbb.2008.10.016. Epub 2008 Oct 31.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Validation Study

MeSH terms

  • Administration, Cutaneous
  • Adult
  • Analysis of Variance
  • Biomarkers
  • Cotinine / blood
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Nicotine / administration & dosage
  • Nicotine / pharmacokinetics*
  • Nicotine / therapeutic use*
  • Nicotinic Agonists / administration & dosage
  • Nicotinic Agonists / pharmacokinetics*
  • Nicotinic Agonists / therapeutic use*
  • Predictive Value of Tests
  • ROC Curve
  • Smoking Cessation / statistics & numerical data*
  • Treatment Outcome


  • Biomarkers
  • Nicotinic Agonists
  • Nicotine
  • Cotinine