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Nicotine pharmacokinetics and subjective effects of three potential reduced exposure products, moist snuff and nicotine lozenge
  1. Michael Kotlyar1,
  2. M Irene Mendoza-Baumgart2,
  3. Zhong-ze Li3,
  4. Paul R Pentel2,
  5. Brianne C Barnett2,
  6. Rachel M Feuer2,
  7. Erin A Smith2,
  8. Dorothy K Hatsukami2
  1. 1Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA
  2. 2Transdisciplinary Tobacco Use Research Center, University of Minnesota, Minneapolis, Minnesota, USA
  3. 3Biostatistics Core, Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA
  1. Correspondence to:
 Dr M Kotlyar
 College of Pharmacy, University of Minnesota, 7-170 Weaver Densford Hall, 308 Harvard Street SE, Minneapolis, MN 55455, USA; kotly001{at}


Objective: To compare nicotine pharmacokinetics and subjective effects of three new smokeless tobacco potential reduced exposure products (PREPs; Ariva, Revel and Stonewall) with moist snuff (Copenhagen) and medicinal nicotine (Commit lozenge).

Methods: 10 subjects completed a randomised, within-subject, crossover study. Subjects used one product for 30 min at each of the five laboratory sessions. Maximal nicotine concentration (Cmax) was determined and area under the concentration time curve (AUC) was calculated for a 90-min period (during use and 60 min after use). Nicotine craving, withdrawal symptoms and ratings of product effects and liking were measured during product use.

Results: Nicotine AUC and Cmax were higher for Copenhagen than for any other product (p<0.002) and higher for Commit than for either Ariva or Revel (p<0.001). Cmax for Commit was also higher than for Stonewall (p = 0.03). Craving was lowest during use of Copenhagen (p<0.03). Craving during use of Stonewall, Ariva and Commit was lower than during use of Revel (p<0.05). Withdrawal symptom score during use of Copenhagen was lower than during use of Revel (p = 0.009). Copenhagen scores were higher (p<0.005) than all other products in several measures of drug effects and liking (feel good effects, satisfaction, liking and desire for product, and strength of product).

Conclusion: The new smokeless tobacco PREPs result in lower nicotine concentrations and equivalent or lower reductions in subjective measures compared with medicinal nicotine. Since health effects of PREPs are largely unknown, medicinal nicotine should be preferentially encouraged for smokers or smokeless tobacco users wishing to switch to lower-risk products.

  • AUC, area under the concentration–time curve
  • Cmax, maximal nicotine concentration
  • PREP, potential reduced exposure product
  • Tmax, maximal tobacco concentration

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  • Funding: This study was supported by grant # P50DA013333 (Transdisciplinary Tobacco Use Research Center), grant # K23DA017307 and grant # M01-RR00400 (General Clinical Research Center Program).

  • Competing interests: None.