A Randomised, Crossover, Clinical Study to Assess Nicotine Pharmacokinetics and Subjective Effects of the BIDI Stick ENDS Compared with Combustible Cigarettes and a Comparator ENDS in Adult Smokers

Background: Nicotine pharmacokinetic assessments of electronic nicotine delivery systems (ENDS) are crucial to understand their ability to provide an alternative to cigarette smoking. Subjective effects data also strongly contribute to this understanding. The BIDI® Stick is a disposable ENDS product which contains 6% nicotine benzoate salt and various flavours. Methods: In this study we assessed nicotine pharmacokinetic and subjective effects of BIDI® Stick ENDS in adult smokers, compared to cigarettes and a comparator ENDS product. During each of eight (8) study visits, volunteer smoker subjects randomly used one of either their usual brand (UB) of cigarette, a BIDI® Stick ENDS, or a comparator ENDS (JUUL 5% with Virginia Tobacco flavour), during both defined (10 puffs, 30 seconds apart) and ad libitum puffing sessions. Blood samples were collected at various time points and subjective effects questionnaires were administered. Results: Plasma nicotine Cmax 0-120 was not significantly different between BIDI® Stick ENDS with any flavour (range 15.3 (9.90) ng/ml for BIDI® Stick Winter to 17.6 (9.00) ng/ml for BIDI® Stick Classic) and UB cigarettes [16.2 (9.17) ng/ml]. AUC0-120 and Tmax 0-120 values were also not significantly different between BIDI® Stick ENDS and UB cigarettes, while subjective effects measures were also similar between BIDI® Stick ENDS and UB cigarettes. Conclusions: BIDI® Stick ENDS delivered nicotine to users comparably to their UB combustible cigarette and also elicited similar subjective effects such as satisfaction and relief. Thus, the BIDI® Stick ENDS may be a satisfying alternative to cigarettes among current smokers and may support their transitioning away from cigarette smoking. Trial registration: ClinicalTrials.gov (identifier number NCT05072925).

A randomised controlled single-centre open-label pharmacokinetic study to examine various approaches of nicotine delivery using electronic cigarettes

Smokers who switch completely to e-cigarettes may reduce their relative risk of tobacco-related disease. Effective nicotine delivery from e-cigarettes is important in consumer acceptance. We assessed whether protonated nicotine and e-cigarette devices delivering greater aerosol mass increase nicotine delivery and product liking. A randomised controlled non-blinded eight-arm crossover study was used to assess plasma nicotine pharmacokinetics and product liking for two e-cigarettes (Vype ePen3 and Vype ePen) with various nicotine e-liquid formulations and a conventional cigarette among 24 healthy dual-users of cigarettes and e-cigarettes. Product use and puff count were also assessed. Results show that nicotine bioavailability was greater for Vype ePen3 with greater aerosol mass delivery than for Vype ePen (Cmax, p = 0.0073; AUC0–120 min, p = 0.0102). Protonated nicotine (18 mg/mL, medium protonation) e-liquid yielded higher nicotine bioavailability than unprotonated nicotine (18 mg/mL) e-liquid (Cmax, p = 0.0001; AUC0–120 min, p = 0.0026). There was no significant difference in Tmax between e-liquids. Nicotine bioavailability did not differ between nicotine benzoate formulation (30 mg/mL nicotine, high protonation) and combustible cigarettes (Cmax, p = 0.79; AUC0–120 min, p = 0.13). Vype ePen3 with protonated nicotine delivers nicotine more efficiently with the potential to increase product liking relative to earlier devices using unprotonated e-liquid.