Nicotine metabolite ratio predicts smoking topography: The Pennsylvania Adult Smoking Study

Drug Alcohol Depend. 2018 Sep 1;190:89-93. doi: 10.1016/j.drugalcdep.2018.06.003. Epub 2018 Jul 4.


Background: The nicotine metabolite ratio (NMR) as measured by the ratio of 3'hydroxycotinine to cotinine has been examined in relation to tobacco use patterns including cigarettes per day and quit success to determine its role in nicotine dependence. We examined the NMR in relation to smoking topography and tested the hypothesis that normal metabolizers have a greater total daily puff volume than slow metabolizers.

Methods: The Pennsylvania Adult Smoking Study (PASS) is a longitudinal study of 352 adults who smoked, on average, 17 cigarettes per day. Subjects used a portable smoking topography device over a two-day period at home and at work. We measured the ratio of 3'hydroxycotinine to cotinine in the saliva of the subjects.

Results: In multiple linear regression analyses, a higher rate of nicotine metabolism was significantly associated with increased daily puffs and total daily puff volume. In a mediation analysis, a significant, indirect effect of race on the relationship between NMR and puff volume was observed, with 22% of the effect mediated by white race. A higher NMR was also associated with female gender, white race, cigarettes per day and nicotine dependence measures.

Conclusion: The NMR was associated with tobacco use patterns including smoking topography. Faster nicotine metabolism was associated with greater total daily puffs and puff volume.

Keywords: Cotinine; Dependence; Nicotine metabolism; Nicotine metabolite ratio; Smoking; Smoking topography.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cotinine / analogs & derivatives
  • Cotinine / analysis
  • Cotinine / metabolism
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Nicotine / analysis
  • Nicotine / metabolism*
  • Pennsylvania / epidemiology
  • Predictive Value of Tests
  • Saliva / chemistry
  • Tobacco Products
  • Tobacco Smoking*
  • Tobacco Use Disorder / diagnosis*
  • Tobacco Use Disorder / epidemiology
  • Tobacco Use Disorder / metabolism*


  • hydroxycotinine
  • Nicotine
  • Cotinine