Pharmacokinetic Comparison of a Novel Non-tobacco-Based Nicotine Pouch (ZYN) With Conventional, Tobacco-Based Swedish Snus and American Moist Snuff

Abstract

The single dose pharmacokinetics of a novel, non-tobacco-based nicotine pouch, ZYN®, 3 and 6 mg, were compared to 8 mg General snus (Part 1) and ZYN® 8 mg was compared to 18 mg Longhorn moist snuff (Part 2). Methods A single-dose randomized cross-over design was used. In-vivo extraction and pharmacokinetic parameters were determined. Results Part1. The AUCinf of ZYN® 3mg was 27% smaller than that of 8mg General and the AUCinf of ZYN® 6 mg was 34% larger than that of 8mg General. Less nicotine was extracted from ZYN® 3 mg (1.5 mg) and more from ZYN® 6 mg (3.5 mg)than from 8mg General (2.4 mg). The extracted fractions of nicotine for both ZYN® products (56% and 59%) were significantly larger than for 8mg General (32%). Results Part 2. Close to identical plasma nicotine curves, AUCinf and Cmax were found for ZYN® 8 mg and Longhorn Natural 18 mg moist snuff. The extracted amount of nicotine from ZYN® 8 mg (3.8 mg) was larger than the amount extracted from Longhorn Natural 18 mg (3.0 mg, but smaller than the extracted amount of nicotine from General 2x8 mg snus pouches (5.0 mg). The extracted fraction of nicotine for ZYN® 8 mg (50%) was larger than for Longhorn Natural (19%) and General 2x8mg snus pouches (33%). Conclusions The two higher doses of ZYN (6 mg and 8 mg) deliver nicotine as quickly and to a similar extent as existing smokeless products, with no significant adverse effects. Implications The present study demonstrates the characteristics of three strengths of a novel tobacco-free oral snus, ZYN®, viz. the extraction of nicotine from the oral cavity and its uptake into the systemic blood circulation. Comparison is made to Swedish General® snus and American Longhorn® moist snuff and from literature 4 mg Nicorette® gum and 13 brands of e-cigarettes.

A Randomised Study to Investigate the Nicotine Pharmacokinetics of Oral Nicotine Pouches and a Combustible Cigarette

“…Like snus, NPs are placed between the user's upper lip and the gum [19], where the nicotine released is absorbed into the blood through the oral mucosa. Unlike snus, however, NPs typically do not contain tobacco but pharmaceutical grade nicotine absorbed onto a cellulose matrix in a porous pouch [19][20][21]. The comparatively simple composition of NPs relative to snus is reflected in a recent toxicant analysis, which showed that NPs contain lower levels than snus of 10 harmful and potentially harmful tobacco constituents (HPHCs) and undetectable levels of a further 13 HPHCs [20].…”

Heated Tobacco Products and Nicotine Pouches: A Survey of People with Experience of Smoking and/or Vaping in the UK

“…One study compared pharmacokinetics of ZYN with two other oral products, snus (tobacco pouches) and wet snuff (chewing tobacco). Results indicated that ZYN could deliver nicotine into the bloodstream as quickly and to a similar extent as the existing smokeless products with no significant adverse effects [17]. For Zonnic, an older type of nicotine pouch, trials found that compared with nicotine gum, nicotine pouches were as effective or more effective at reducing craving and favoured by smokers [18,19].…”

Chemical characterization of tobacco-free “modern” oral nicotine pouches and their position on the toxicant and risk continuums

“…However, for compounds that show significantly less extraction than nicotine such as metals (Cuello-Nuñez et al 2018), these estimations should be viewed as conservative. Using reported nicotine extraction of 44-72% for gum NRT (Benowitz et al 1987, Lunell and Lunell 2005a, Lunell and Curvall 2011, Digard et al 2013a, Hansson et al 2019, 30-39% for snus (Lunell and Lunell 2005a, Caraway and Chen 2013, Digard et al 2013a, b, Lunell et al 2020, and 56% and 59% for NPs (Lunell et al 2020), we calculated average f EU values of 0.62, 0.33 and 0.58 for gum, snus and NPs, respectively; in addition, we assumed f EU ¼ 1 for the lozenge NRT, which dissolves completely in the user's mouth. These f EU values were assigned to the extraction of all toxicants except for metals from snus, which have been established as having extraction efficiencies of 10% or less (Lunell andLunell 2005b, Caraway andChen 2013); we therefore used f EU ¼ 0.1 for cadmium, nickel and mercury, and conservative estimates of f EU ¼ 0.05 for arsenic, chromium and lead (Supplementary Table 2).…”