Nicotine metabolite ratio as a predictor of cigarette consumption

Nicotine Tob Res. 2003 Oct;5(5):621-4. doi: 10.1080/1462220031000158717.


The rate of nicotine metabolism is hypothesized to be a determinant of how much a person smokes. That is, rapid metabolizers would be expected to need more nicotine and, therefore, smoke more than slow metabolizers. Nicotine is metabolized extensively by the liver enzyme CYP2A6, primarily to cotinine. Cotinine is itself metabolized by CYP2A6 to 3'-hydroxycotinine (3-HC). The ratio of metabolite to parent (i.e., 3-HC:cotinine) would be expected to reflect CYP2A6 activity. We measured the ratio of 3-HC:cotinine in the urine of 72 smokers. This ratio was significantly correlated with the number of cigarettes smoked per day (r=.33, p=.005), though not with the Fagerström Test for Nicotine Dependence. This finding supports the hypothesis that the rate of nicotine metabolism is a determinant of the level of cigarette consumption and supports the use of the 3-HC:cotinine ratio as a noninvasive marker of nicotine metabolism.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Biomarkers / analysis*
  • Cotinine / analogs & derivatives*
  • Cotinine / urine*
  • Female
  • Ganglionic Stimulants / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Nicotine / metabolism*
  • Predictive Value of Tests
  • Sensitivity and Specificity
  • Smoking*
  • Tobacco Use Disorder / diagnosis*


  • Biomarkers
  • Ganglionic Stimulants
  • hydroxycotinine
  • Nicotine
  • Cotinine