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 (C max ) 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 C max 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). C max 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.

Background: The ratio of two nicotine metabolites, cotinine and trans-3 ¶-hydroxycotinine (3-HC), has been validated as a method of phenotyping the activity of the liver enzyme cytochrome P450 (CYP) 2A6 and, thus, the rate of nicotine metabolism. Our objective was to evaluate the correlates and stability of the 3-HC to cotinine ratio in ad libitum and reducing smokers, using nicotine replacement therapy (NRT), over a period of months. Methods: Smokers (n = 123, 94% Caucasian) participated in a smoking reduction study, where one-third of the sample smoked ad libitum for 8 weeks (Waitlist phase), before joining the rest of the participants for 12 weeks of cigarette reduction (Reduction phase) using NRT. Urinary nicotine, cotinine, and 3-HC were measured at each visit. Results: The baseline 3-HC to cotinine ratio was significantly but weakly correlated with cigarettes per