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

Lunell, Erik, Fagerström, Karl, Hughes, John, Pendrill, Robert·2020·Nicotine & Tobacco Research
DOI 10.1093/ntr/ntaa068
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Abstract

Introduction: The single-dose pharmacokinetics (PK) of a novel, non-tobacco-based nicotine pouch, ZYN, 3 and 6 mg, were compared with 8 mg General snus (part 1) and ZYN 8 mg was compared with 18 mg Longhorn moist snuff (part 2). 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 mean of 13 brands of e-cigarettes. Aims and Methods: A single-dose randomized crossover design was used. In vivo extraction and PK parameters were determined. Results: Part 1. The AUCinf of ZYN 3 mg was 27% smaller than that of 8 mg General and the AUCinf of ZYN 6 mg was 34% larger than that of 8 mg General. Less nicotine was extracted from ZYN 3 mg (1.5 mg) and more from ZYN 6 mg (3.5 mg) than from 8 mg General (2.4 mg). The extracted fractions of nicotine for both ZYN products (56% and 59%) were significantly larger than for 8 mg 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 2 × 8 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 2 × 8 mg snus pouches (33%). Conclusions: The two higher doses of ZYN (6 and 8 mg) deliver nicotine as quickly and to a similar extent as existing smokeless products, with no significant adverse effects.

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Crossref · 10.1093/ntr/ntaa068

Cites

9 of 9 references verified0 citation errors · 0 not checkable

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  • Snuff without tobacco gives a similar nicotine absorption to snuff that contains tobacco.

    “Snuff without tobacco has been reported to give a similar nicotine absorption to snuff (or snus) that contains tobacco. 13”

    From Decreased sperm counts in Swedish users of oral tobacco (2022) · cites this paper as [13]

  • To the authors' knowledge, only one study has reported the nicotine pharmacokinetics for NPs.

    “to our knowledge, only one study has reported the nicotine pharmacokinetics for NPs [21].”

    From A Randomised Study to Investigate the Nicotine Pharmacokinetics of Oral Nicotine Pouches and a Combustible Cigarette (2022) · cites this paper as [21]

  • The results for the 10 mg Zyn NP contrast with those published by Lunell et al., who reported similar Cmax (18.5 ng/mL) and AUC∞ (58.4 ng·h/mL) values for an 8 mg Zyn NP to the highest values observed in this study (Cmax 18.4 ng/mL and AUC0-6h/AUC∞ 53.7/64.3 ng·h/mL).

    “Notably, the results for the 10 mg Zyn NP contrast with those published by Lunell et al. [21], who reported similar Cmax (18.5 ng/mL) and AUC∞ (58.4 ng·h/mL) values for an 8 mg Zyn NP to the highest values observed in this study (Cmax 18.4 ng/mL and AUC0–6h /AUC∞ 53.7/64.3 ng·h/mL).”

    From A Randomised Study to Investigate the Nicotine Pharmacokinetics of Oral Nicotine Pouches and a Combustible Cigarette (2022) · cites this paper as [21]

  • The extraction of nicotine from NPs during use appears to be greater than the extraction of nicotine from snus; 58% on average over 60 min compared with 33% on average from snus.

    “The extraction of nicotine from NPs during use appears to be greater than the extraction of nicotine from snus; 58% on average over 60 min [21] compared with 33% on average from snus [20].”

    From A Randomised Study to Investigate the Nicotine Pharmacokinetics of Oral Nicotine Pouches and a Combustible Cigarette (2022) · cites this paper as [21]

  • In Lunell et al., an NP with a nicotine content of 6 mg resulted in greater AUC compared with Swedish snus with a nicotine content of 8 mg.

    “Lunell et al. [21] compared the nicotine pharmacokinetics between NPs and snus among snus users, and found that an NP with a nicotine content of 6 mg resulted in greater AUC as compared with Swedish snus with a nicotine content of 8 mg”

    From A Randomised Study to Investigate the Nicotine Pharmacokinetics of Oral Nicotine Pouches and a Combustible Cigarette (2022) · cites this paper as [21]

Cites

Flagged first, then by citations

1 of the 10 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Plurphanswat Hughes, 2020, Initial information on a novel nicotine product [published online ahead of print March 16, 2020]
  2. Digard, 2009, Patterns and behaviors of snus consumption in Sweden, Nicotine Tob Res., 11, 1175, 10.1093/ntr/ntp118 · DOI · Paper page

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Authors
Lunell, E., Fagerström, K., Hughes, J., & Pendrill, R.
Affiliations
  • Department of Clinical Pharmacology, CROEL AB, Helsingborg, Sweden
  • Uppsala University (SE)
  • University of Vermont (US)
  • Swedish Match AB (publ) (Sweden) (SE)
Corresponding author
Lunell, Erik
ORCID
Venue
Nicotine & Tobacco Research
Publisher
Oxford University Press (OUP)
Published
2020-04-22
Volume
22
Issue
10
Pages
1757-1763
ISSN
  • 1462-2203 (ISSN-L)
  • 1469-994X
DOI
10.1093/ntr/ntaa068
OpenAlex
W3016972223
Semantic Scholar
4895b847915595e0380fc3c045530aa40dec5178
Cited by
121
References
10
Citations by year
2026: 30 · 2025: 25 · 2024: 15 · 2023: 9 · 2022: 22 · 2021: 18 · 2020: 2
FWCI
7.43
Type
journal article
Language
en
Open access
closed
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • Nicotine & Tobacco Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
Swedish Match AB
Topics
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
Keywords
nicotine pouches, snus, moist snuff, nicotine pharmacokinetics, nicotine extraction, nicotine delivery, smokeless tobacco
MeSH terms
Adult, Female, Humans, Male, Nicotine, Sweden, Tissue Distribution, Tobacco, Smokeless, United States, Cross-Over Studies, Young Adult, Tobacco Use, Electronic Nicotine Delivery Systems

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