Nicotine pharmacokinetics and subjective response among adult smokers using different flavors of on!® nicotine pouches compared to combustible cigarettes

Rensch, Jesse; Liu, Jianmin; Wang, Jingzhu; Vansickel, Andrea R.; Edmiston, Jeffery; Sarkar, Mohamadi

doi:10.1007/s00213-021-05948-y

Cited by 25 publications

(35 citation statements)

References 31 publications

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“…3b). Also, in a previous study, we observed a higher mean C max for OBCs was 17.7 ng/mL (Rensch et al 2021), than that observed in this study (12.2 ng/mL). Similarly, the mean C max values observed with OBMST (9.8 mg/mL) were lower than those reported in published literature (range of 12 to 19 ng/mL; Benowitz and Gourlay 1997;Benowitz et al 1988;Fant et al 1999;Kotlyar et al 2007;Pickworth et al 2014).…”

Section: Discussioncontrasting

confidence: 74%

“…Results of this partial single-blind, randomized, 7-way crossover study suggest that, among current AS and MST users, the abuse potential of NPs tested is not likely to be higher than cigarette or MST. The study results and literature reported PK values for cigarettes (D'Ruiz et al 2015;Goldenson et al 2020;O'Connell et al 2019;Phillips-Waller et al 2021;Picavet et al 2016;Rensch et al 2021;Stiles et al 2018;Voos et al 2019;Yuki et al 2017) and MST (Benowitz et al 1988;Digard et al 2013;Fant et al 1999;Kotlyar et al 2007;Lunell et al 2020;Pickworth et al 2014) indicate that the nicotine delivery and subjective effects of NPs tested are not likely to be greater than cigarette or MST.…”

Section: Discussionmentioning

confidence: 54%

“…The authors concluded that based on the PK profiles and subjective responses, the NPs were likely to be associated with lower abuse potential than cigarettes. The findings from the study also indicated that flavor does not appear to influence nicotine PK or subjective responses, and the NPs may be potentially acceptable switching products for AS and adult MST users (Rensch et al 2021 ). We present here results from a randomized, controlled, clinical study with varying nicotine levels to further inform the abuse potential of the on!® NPs.…”

Section: Introductionmentioning

confidence: 94%

“…To date, there are only two published studies that inform the abuse potential of NPs (Lunell et al 2020 ; Rensch et al 2021 ). Lunell et al ( 2020 ) compared Zyn® NPs containing 3 and 6 mg nicotine with 8 mg General snus, and Zyn® NPs containing 8 mg nicotine with 18 mg Longhorn moist snuff in a study of snus users.…”

Section: Introductionmentioning

confidence: 99%

“…The authors observed that the two higher levels of Zyn® (6 and 8 mg) delivered nicotine as quickly and to a similar extent as the comparator MST. The authors had also measured subjective effects (“head buzz”) and observed no obvious correlation between nicotine levels and the maximum score for “head buzz.” Rensch et al recently reported nicotine pharmacokinetics (PK) and subjective effects of six flavors of on!® NPs containing 4 mg nicotine in AS compared to own brand cigarettes ( 2021 ). This study was specifically designed to assess abuse potential of the NPs investigated relative to cigarettes.…”

Section: Introductionmentioning

confidence: 99%

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Nicotine pharmacokinetics and subjective responses after using nicotine pouches with different nicotine levels compared to combustible cigarettes and moist smokeless tobacco in adult tobacco users

et al. 2022

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Rationale Oral tobacco–derived nicotine products include on!® nicotine pouches (NPs) which are tobacco-leaf free and available in multiple flavors and nicotine levels. Switching completely to NPs from cigarettes and moist smokeless tobacco (MST) has the potential to reduce harm for adult tobacco consumers. However, the dependence potential of NPs is not established. Therefore, we characterized the abuse potential of NPs with different nicotine levels compared to cigarettes and MST. Objectives To evaluate nicotine pharmacokinetics (PK) and subjective effects of NPs (ranging from 1.5 to 8 mg nicotine) compared to own brand cigarettes (OBCs) and MST (OBMST). Methods We used a randomized, in-clinic, partial single-blind, 7-way crossover design to assess nicotine PK and subjective effects in dual users of cigarettes and MST. Results The mean nicotine Cmax for NPs increased with nicotine level, ranging from 3.5 ng/mL (1.5 mg NP) to 15.4 ng/mL (8 mg NP), compared with 12.2 ng/mL for OBCs and 9.8 ng/mL for OBMST. Nicotine tmax was much longer for all NPs and OBMST (32.5–34.4 min) compared to OBCs (8.5 min). Reductions in urges to smoke after use of the 2 mg, 3.5 mg, and 8 mg NPs were not statistically different (p > 0.05) relative to OBC. Also, NPs resulted in lower ratings of positive subjective effects relative to OBCs and OBMST. Conclusions Overall, based on the study results and literature reported nicotine PK values for cigarettes and MST, the abuse potential of NPs is not likely to be higher than OBCs and OBMST. NPs may be potentially acceptable switching products for users of cigarettes and MST products.

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Section: Discussioncontrasting

confidence: 74%

Section: Discussionmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nicotine pharmacokinetics and subjective responses after using nicotine pouches with different nicotine levels compared to combustible cigarettes and moist smokeless tobacco in adult tobacco users

et al. 2022

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A Randomized, Controlled Study to Assess Changes in Biomarkers of Exposures Among Adults Who Smoke That Switch to Oral Nicotine Pouch Products Relative to Continuing Smoking or Stopping All Tobacco Use

Rensch

Edmiston

Wang

et al. 2023

The Journal of Clinical Pharma

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The purpose of this open‐label, randomized, controlled, in‐clinic, 5‐parallel‐group study was to assess biomarkers of exposure (BoE) to select harmful and potentially harmful constituents in adults who smoke (N = 144) switching to oral tobacco products (on!® mint nicotine pouches; test products) compared to continuing smoking cigarettes (CS) and completely quitting all tobacco products (NT). Changes in 20 BoE to select harmful and potentially harmful constituents, including 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol (NNAL), were evaluated. Adult smokers smoked their usual brand of cigarettes for 2 days (baseline assessments) and then were randomly assigned to ad libitum use of 2, 4, or 8 mg test products, CS, or NT for 7 days. Analysis of covariance was used to assess the Day 7 BoE levels between each group using test products, CS, and NT. The creatinine‐adjusted total urinary NNAL and other 18 of 19 BoE levels (except nicotine equivalents [NEs]) were significantly lower (P < .05) on Day 7, among all test product groups compared to CS. Geometric least‐square means were reduced for all biomarkers of exposure, except NEs, in test product groups by approximately 42%–96% compared to the CS group, and reductions were comparable to the NT group. The geometric least‐square means for urinary NE between the test product and the CS groups, although not significantly different, the Day 7 mean change relative to the CS group were 49.9%, 65.8%, and 101% for the 2, 4, and 8 mg test product groups, respectively. The substantial reduction in harmful and potentially harmful constituent exposure suggests complete switching from cigarettes to test products may present a harm reduction opportunity for adults who smoke.

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A randomised, open-label, cross-over clinical study to evaluate the pharmacokinetic, pharmacodynamic and safety and tolerability profiles of tobacco-free oral nicotine pouches relative to cigarettes

et al. 2022

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Rationale Tobacco harm reduction (THR) involves encouraging adult smokers who would otherwise continue to smoke to transition to less harmful forms of nicotine delivery. These products must offer adult smokers reduced exposure to chemicals associated with tobacco combustion, satisfactory blood plasma nicotine levels and serve as an acceptable alternative. The most recent THR innovation is tobacco-free oral nicotine pouches. Objectives This study aimed to compare pharmacokinetic, pharmacodynamic and safety and tolerability profiles of two nicotine pouch variants (ZoneX #2 (5.8 mg nicotine/pouch); ZoneX #3 (10.1 mg nicotine/pouch)) with cigarette to assess the pouches’ THR potential. Methods This was a controlled use, randomised, open-label, cross-over clinical study with 24 healthy adult traditional tobacco users. Pharmacokinetic (plasma nicotine levels; up to 8 h post-use), pharmacodynamic (urge to smoke, product liking; up to 4 h post-use) and short-term safety and tolerability profiles were assessed. Results Distinct nicotine pouch pharmacokinetic profiles indicated nicotine absorption via the oral mucosa. Plasma nicotine levels were lower, and time to peak slower, for the nicotine pouches compared to cigarette (Cmax cigarette: 11.6 ng/ml vs. #2: 5.2 ng/ml, p < 0.0001; #3: 7.9 ng/ml, p < 0.0003) (Tmax cigarette: 8.6 min vs. #2: 26 min; #3: 22 min). All products effectively reduced subjects’ urge to smoke and presented favourable product liking scores; nicotine pouches were also well tolerated following short-term use (no serious adverse events). Conclusions Overall, the assessed ZoneX nicotine pouches may offer an acceptable alternative for adult smokers to achieve satisfactory levels of nicotine delivery and, based on the pharmacokinetic parameters and under the study conditions, likely have a lower abuse liability and addictive potential for current adult smokers compared to continued cigarette smoking. Clinical trial identifier: NCT04891406 (clinicaltrials.gov).

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Nicotine pharmacokinetics and subjective response among adult smokers using different flavors of on!® nicotine pouches compared to combustible cigarettes

Cited by 25 publications

References 31 publications

Nicotine pharmacokinetics and subjective responses after using nicotine pouches with different nicotine levels compared to combustible cigarettes and moist smokeless tobacco in adult tobacco users

Nicotine pharmacokinetics and subjective responses after using nicotine pouches with different nicotine levels compared to combustible cigarettes and moist smokeless tobacco in adult tobacco users

A Randomized, Controlled Study to Assess Changes in Biomarkers of Exposures Among Adults Who Smoke That Switch to Oral Nicotine Pouch Products Relative to Continuing Smoking or Stopping All Tobacco Use

A randomised, open-label, cross-over clinical study to evaluate the pharmacokinetic, pharmacodynamic and safety and tolerability profiles of tobacco-free oral nicotine pouches relative to cigarettes

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