Nicotine pharmacokinetics and subjective effects of three potential reduced exposure products, moist snuff and nicotine lozenge

Abstract

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.

A pilot randomized study of smokeless tobacco use among smokers not interested in quitting: Changes in smoking behavior and readiness to quit

“…This suggests that Ariva and Stonewall are effective products to curb withdrawal and craving. In support of this interpretation, we found no changes in overall craving or withdrawal as smokers substituted Ariva/ Stonewall for cigarettes, which is generally consistent with reports from others (Blank, Sams, Weaver, & Eissenberg, 2008;Kotlyar et al, 2007;Mendoza-Baumgart et al, 2007). However, although cigarettes per day significantly decreased among smokers who used Ariva/Stonewall, reduction in CO was less striking (6%), suggesting partial compensation (e.g., inhaling deeper, more frequent puffs) and/or problems with the use of CO as a biomarker of tobacco exposure in this population (see following).…”

Nicotine delivery, cardiovascular profile, and subjective effects of an oral tobacco product for smokers

“…In this study, one tablet did not increase plasma nicotine concentration reliably. However, in a study of SLT users (Kotlyar et al, 2007), one tablet produced significant increases in maximum nicotine concentration (Cmax). By way of comparison, a single cigarette can increase mean plasma nicotine concentration by 5-14 ng/ml (Benowitz et al, 1988;Breland et al, 2006).…”

“…Some of these products have been analyzed to determine tobacco-specific nitrosamine (TSNA) content, and the mean level of TSNAs in Ariva was lower than that found in Exalt, Revel, and smokeless tobacco products typically marketed in the United States (Stepanov, Jensen, Hatsukami, & Hecht, 2006). Another study examined Ariva's effects in smokeless tobacco (SLT) users and found that one tablet delivered nicotine (Cmax 5 2.7 ng/ml; 95% CI 5 2.0-3.6) and reduced craving over a 30-min period (Kotlyar et al, 2007). However, nicotine exposure may differ in SLT users from that of smokers (Benowitz, Porchet, Sheiner, & Jocob, 1988), Ariva's intended audience.…”

Dependence on Tobacco and Nicotine Products: A Case for Product-Specific Assessment

“…Their impact on the market has been relatively small so far. Generally , they seem to give rise to lower blood nicotine concentrations ( Gray, Breland, Weaver, & Eissenberg, 2008 ;Kotlyar et al, 2007 ) than the traditional ST products -snus and chewing tobacco. The fi lm is tucked to , for example, the palate and will dissolve by itself , while the stick and the orb (tablet) can be manipulated and sucked.…”