Nicotine pharmacokinetics of electronic cigarettes: a review of the literature

Introduction:
This article provides a comprehensive review of the literature on nicotine pharmacokinetics of electronic cigarettes. It discusses 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. The review also highlights current research gaps and the potential utility of modelling and standardization of methodologies used to assess nicotine delivery.

Key Points:

* E-cigarettes are battery-powered electronic devices that aerosolise a solution, often called an e-liquid, which either contains nicotine or is nicotine-free.
* E-cigarette liquid (e-liquid) is held in a reservoir and typically contains nicotine, propylene glycol (PG), vegetable glycerine (VG), water and flavourings in differing relative amounts.
* E-cigarettes have evolved from generally disposable 'cig-a-like' products to more recent 'mods' or 'modular' products that are typically comprised of separate battery, reservoir and atomiser components.
* E-cigarette nicotine pharmacokinetic studies have been performed for a number of years and are beginning to show how nicotine delivery is evolving as the products themselves evolve.
* Nicotine pharmacokinetic studies provide information on the time-course of a drug or other chemical compound, and most commonly focus on the absorption of nicotine.
* The study design is broadly the same in nicotine pharmacokinetic studies: volunteer subjects use the product under a study-specific set of conditions, and blood samples collected before, during and after product use are taken at set time points.
* The plasma fraction of these blood samples is then assayed for nicotine levels using standardized bioanalytical methodologies, most commonly by mass spectrometry.
* Commonly, alongside these bioanalytical measurements, assessments are made of subjective measures such as product liking, craving, urge to smoke and/or withdrawal symptoms.

Main Message:
The article highlights the importance of understanding nicotine delivery from e-cigarettes, particularly in the context of their potential role in tobacco harm reduction. From a regulatory perspective, greater knowledge and understanding of nicotine delivery from e-cigarettes could help to inform the assessment of abuse liability. Nicotine pharmacokinetic studies, in combination with subjective effects data, would inform an overall evaluation of the abuse liability of e-cigarettes. abuse liability is generally considered to be higher in combusted products compared to non-combusted tobacco and nicotine products that have a slower and/or lower nicotine delivery due to the lower efficiency of nicotine uptake via routes other than inhalation, such as through the skin or via the buccal cavity. The overall assessment of abuse liability is important since one of the concerns raised against the widespread commercial availability of e-cigarettes is the potential that they merely substitute one form of nicotine addiction for another and lead to sustained use of e-cigarettes, cigarettes, or both.

Fearon, Ian M., alison C. Eldridge, Nathan Gale, Mike McEwan, Mitchell F. Stiles, and Elaine K. Round. “Nicotine Pharmacokinetics of Electronic Cigarettes: a Review of the Literature.” Regulatory Toxicology and Pharmacology 100 (December 2018): 25–34. https://doi.org/10.1016/j.yrtph.2018.09.004.