Impact of e-liquid flavors on nicotine intake and pharmacology of e-cigarettes

Gideon St Helen¹, Delia A Dempsey², Christopher M Havel², Peyton Jacob 3rd³, Neal L Benowitz⁴

Affiliations

¹ Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, University of California, San Francisco, CA, USA; Center for Tobacco Control Research and Education, University of California, San Francisco, CA, USA; Tobacco Center of Regulatory Science (TCORS), University of California, San Francisco, CA, USA. Electronic address: Gideon.Sthelen@ucsf.edu.
² Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, University of California, San Francisco, CA, USA.
³ Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, University of California, San Francisco, CA, USA; Center for Tobacco Control Research and Education, University of California, San Francisco, CA, USA; Tobacco Center of Regulatory Science (TCORS), University of California, San Francisco, CA, USA.
⁴ Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, University of California, San Francisco, CA, USA; Center for Tobacco Control Research and Education, University of California, San Francisco, CA, USA; Tobacco Center of Regulatory Science (TCORS), University of California, San Francisco, CA, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.

PMID: 28704768
PMCID: PMC5565733
DOI: 10.1016/j.drugalcdep.2017.05.042

Impact of e-liquid flavors on nicotine intake and pharmacology of e-cigarettes

Gideon St Helen et al. Drug Alcohol Depend. 2017.

. 2017 Sep 1:178:391-398.

doi: 10.1016/j.drugalcdep.2017.05.042. Epub 2017 Jun 30.

Authors

Gideon St Helen¹, Delia A Dempsey², Christopher M Havel², Peyton Jacob 3rd³, Neal L Benowitz⁴

Affiliations

¹ Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, University of California, San Francisco, CA, USA; Center for Tobacco Control Research and Education, University of California, San Francisco, CA, USA; Tobacco Center of Regulatory Science (TCORS), University of California, San Francisco, CA, USA. Electronic address: Gideon.Sthelen@ucsf.edu.
² Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, University of California, San Francisco, CA, USA.
³ Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, University of California, San Francisco, CA, USA; Center for Tobacco Control Research and Education, University of California, San Francisco, CA, USA; Tobacco Center of Regulatory Science (TCORS), University of California, San Francisco, CA, USA.
⁴ Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, University of California, San Francisco, CA, USA; Center for Tobacco Control Research and Education, University of California, San Francisco, CA, USA; Tobacco Center of Regulatory Science (TCORS), University of California, San Francisco, CA, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.

PMID: 28704768
PMCID: PMC5565733
DOI: 10.1016/j.drugalcdep.2017.05.042

Abstract

Objectives: To describe the effect of e-liquid flavors on nicotine intake and pharmacology of e-cigarettes.

Methods: 11 males and 3 females participated in a 3-day inpatient crossover study with strawberry, tobacco, and their usual flavor e-liquid. Nicotine levels were nominally 18mg/mL in the strawberry (pH 8.29) and tobacco (pH 9.10) e-liquids and ranged between 3-18mg/mL in the usual brands (mean pH 6.80). Each day consisted of a 15-puff session followed by 4h of abstinence, then 90min of ad libitum use. Subjects used a KangerTech mini ProTank 3.

Results: After 15 puffs, the amount of nicotine inhaled and systemically retained were not significantly different between the strawberry and tobacco e-liquids but plasma AUC₍₀_→₁₈₀₎ was significantly higher with the strawberry e-liquid. While not significantly different, C_max was 22% higher and various early time point AUCs to measure rate of rise of nicotine in blood ranged between 17 and 23% higher with the strawberry e-liquid compared to the tobacco e-liquid. During ad libitum use, systemic exposure to nicotine (AUC₍₀_→₉₀₎) was the same for the tobacco and usual brand e-liquids but were both significantly lower than after using the strawberry e-liquid. The usual flavors were more liked and satisfying than the strawberry and tobacco e-liquids.

Conclusion: Flavors influence nicotine exposure through flavor liking, may affect rate of nicotine absorption possibly through pH effects, and contribute to heart rate acceleration and subjective effects of e-cigarettes. E-cigarette users titrate their nicotine exposure but the extent of titration may vary across flavors.

Keywords: E-cigarette pharmacology; E-cigarettes; Flavors; Nicotine delivery; Nicotine pharmacokinetics.

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Conflict of interest statement

Conflict of interest

Dr. Benowitz has served on smoking cessation advisory boards for Pfizer and has been an occasional consultant to McNeil and GlaxoSmithKline, and has served as a paid expert witness in litigation against tobacco companies. All other authors declare that they have no conflicts of interest.

Figures

**Figure 1**
Average plasma nicotine concentration profiles for strawberry and tobacco test e-liquid flavors and usual brand e-liquids (mean ± SEM) after 15 puffs of the standardized session (A); average plasma nicotine concentration profiles for test e-liquid flavors and usual brand e-liquids during 90 minutes of *ad libitum* access to e-cigarettes (B). No differences were observed between strawberry and tobacco test flavors in plot A; open markers in plot B indicate significant differences between strawberry and tobacco test flavors.

**Figure 2**
Within-subject area under the plasma nicotine concentration-time curve from 0 to 90 minutes (AUC_0→90) and mean plasma AUC_0→90 for the strawberry and tobacco test e-liquid flavors and usual brand e-liquids (mean ± SEM) during the 90-minute *ad libitum* session.

See this image and copyright information in PMC

References

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Impact of e-liquid flavors on nicotine intake and pharmacology of e-cigarettes

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Impact of e-liquid flavors on nicotine intake and pharmacology of e-cigarettes

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