Cotinine as a biomarker of systemic nicotine exposure in spit tobacco users

Addict Behav. 2004 Feb;29(2):349-55. doi: 10.1016/j.addbeh.2003.08.046.


Unlike cigarette smokers, spit tobacco (ST) users absorb a significant amount of nicotine through the gastrointestinal tract while swallowing tobacco juice. The majority of the absorbed nicotine is rapidly converted to cotinine during first-pass hepatic metabolism. This process potentially compromises the utility of cotinine as a biomarker for systemic nicotine exposure in ST users. To investigate this question, we correlated nicotine and cotinine concentrations with clinical measures of ST use in 68 daily ST users enrolled in a non-nicotine pharmacologic intervention trial. We found that a higher frequency of swallowing tobacco juice (P=.007) was an independent predictor of higher serum cotinine concentrations. Serum nicotine concentrations, on the other hand, were not correlated with a higher frequency of swallowing. In the absence of a reliable way to measure frequency of swallowing, we conclude that cotinine should not be used for guiding clinical decisions that depend upon a precise quantification of systemic nicotine exposure, such as tailored nicotine replacement therapy.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Cotinine / blood*
  • Deglutition
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nicotine / administration & dosage
  • Nicotine / blood
  • Prospective Studies
  • Tobacco Use Disorder / blood
  • Tobacco Use Disorder / diagnosis*
  • Tobacco, Smokeless / pharmacokinetics*


  • Biomarkers
  • Nicotine
  • Cotinine