Nicotine pharmacokinetics of electronic cigarettes: A review of the literature.

E-cigarettes are battery-powered electronic devices from which users can inhale nicotine following its aerosolisation from a liquid solution. Some regulators and public health bodies consider e-cigarettes as potentially playing a major role in tobacco harm reduction. Their ability to provide nicotine to smokers in both amount and in a manner and form generally similar to cigarette smoking have been proposed as key components to help smokers reduce or cease the use of combustible cigarettes. Nicotine pharmacokinetic studies of e-cigarettes have been performed for a number of years and are beginning to show how nicotine delivery is evolving as the products themselves evolve. In this review, we provide a critical overview of the literature to describe what is known about nicotine delivery from e-cigarettes. We will discuss how the progression of e-cigarette design, development, and user familiarity has allowed increases in nicotine availability to the user, in the context of how much and how rapidly nicotine is delivered during acute-use periods. This review will also provide insight into current research gaps and highlight the potential utility of modelling and the standardisation of methodologies used to assess nicotine delivery to facilitate identification of products that are best suited to displace cigarette smoking among adult smokers.

Switching from usual brand cigarettes to a tobacco-heating cigarette or snus: Part 1. Study design and methodology.

A randomized, multi-center study was conducted to assess potential improvement in health status measures, as well as changes in biomarkers of tobacco exposure and biomarkers of biological effect, in current adult cigarette smokers switched to tobacco-heating cigarettes, snus or ultra-low machine yield tobacco-burning cigarettes (50/group) evaluated over 24 weeks. Study design, conduct and methodology are presented here along with subjects' disposition, characteristics, compliance and safety results. This design and methodology, evaluating generally healthy adult smokers over a relatively short duration, proved feasible. Findings from this randomized study provide generalized knowledge of the risk continuum among various tobacco products (ClinicalTrials.gov Identifier: NCT02061917).

Switching from usual brand cigarettes to a tobacco-heating cigarette or snus: Part 2. Biomarkers of exposure.

A randomized, multi-center study of adult cigarette smokers switched to tobacco-heating cigarettes, snus or ultra-low machine yield tobacco-burning cigarettes (50/group) was conducted, and subjects' experience with the products was followed for 24 weeks. Differences in biomarkers of tobacco exposure between smokers and never smokers at baseline and among groups relative to each other and over time were assessed. Results indicated reduced exposure to many potentially harmful constituents found in cigarette smoke following product switching. Findings support differences in exposure from the use of various tobacco products and are relevant to the understanding of a risk continuum among tobacco products (ClinicalTrials.gov Identifier: NCT02061917).

Switching from usual brand cigarettes to a tobacco-heating cigarette or snus: Part 3. Biomarkers of biological effect.

A randomized, multi-center study of adult cigarette smokers switched to tobacco-heating cigarettes, snus or ultra-low machine yield tobacco-burning cigarettes (50/group) for 24 weeks was conducted. Evaluation of biomarkers of biological effect (e.g. inflammation, lipids, hypercoaguable state) indicated that the majority of consistent and statistically significant improvements over time within each group were observed in markers of inflammation. Consistent and statistically significant differences in pairwise comparisons between product groups were not observed. These findings are relevant to the understanding of biomarkers of biological effect related to cigarette smoking as well as the risk continuum across various tobacco products (ClinicalTrials.gov Identifier: NCT02061917).

Assessment of the abuse liability of three menthol Vuse Solo electronic cigarettes relative to combustible cigarettes and nicotine gum.

RATIONALE: We previously reported that following a short-term product use period, use of non-menthol Vuse Solo electronic cigarettes (ECs) resulted in product effect-related subjective responses and nicotine uptake between those of combustible cigarettes (high-abuse liability comparator) and nicotine gum (low-abuse liability comparator); the results were generally closer to those of nicotine gum. OBJECTIVE: Using a similar design to the previous study, we evaluated the abuse liability of three menthol-flavored Vuse Solo ECs with the same nicotine contents (14, 29, and 36 mg) in a group of EC-naïve, menthol cigarette smokers, relative to comparator products. METHODS: Six-hour nicotine uptake and ratings of subjective effects were used to determine abuse liability and pharmacokinetics. RESULTS: Use of menthol Vuse Solo resulted in significantly lower responses to subjective measurements (product liking, intent to use product again, and liking of positive product effects), higher urge to smoke responses, and a lower peak (Cmax) and overall extent (AUC0-360) of nicotine uptake compared to smoking the usual brand menthol cigarette. When compared with use of nicotine gum, subjective responses to use of menthol Vuse ECs were in the same direction as those resulting from smoking cigarettes but were more similar to nicotine gum use in magnitude than they were to cigarettes. CONCLUSION: These findings are concordant with our previous results and provide evidence that menthol Vuse Solo ECs have abuse liability that is lower than menthol cigarettes and potentially greater than that of nicotine gum. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02664012.

Pharmacodynamic and pharmacokinetic assessment of electronic cigarettes, combustible cigarettes, and nicotine gum: implications for abuse liability.

RATIONALE: Electronic cigarettes (ECs) are becoming popular alternatives for smokers, but there has been limited study of their abuse liability. OBJECTIVES: The objective of this study was to evaluate the abuse liability of three Vuse Solo ECs, ranging from 14 to 36 mg in nicotine content, relative to high- and low-abuse liability comparator products (usual brand combustible cigarettes and nicotine gum, respectively) in a group of 45 EC-naïve smokers. METHODS: Enrolled subjects' ratings of subjective effects and nicotine uptake over 6 h were used to measure abuse liability and pharmacokinetics following in-clinic use of each EC. RESULTS: Use of Vuse Solo resulted in subjective measures and nicotine uptake that were between those of combustible cigarettes and nicotine gum, although generally closer to nicotine gum. Compared to combustible cigarettes, use of Vuse Solo resulted in significantly lower scores in measures of product liking, positive effects, and intent to use again. These pharmacodynamic findings were consistent with the pharmacokinetic data, showing that cigarettes produced substantially faster and higher levels of nicotine uptake as compared to Vuse Solo and nicotine gum. Vuse Solo resulted in more rapid initial uptake of nicotine compared to nicotine gum, but peak concentration and long-term extent of uptake were not different or were lower with Vuse. CONCLUSIONS: Collectively, these findings suggest that Vuse Solo likely has an abuse liability that is somewhat greater than nicotine gum but lower than cigarettes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02269514.