Evaluation of Nicotine Pharmacokinetics among Flavors in Electronic Nicotine Delivery Systems (ENDS): A Parallel, Randomized Study in Two ENDS across Four Flavors

Abstract

Jourhan Lew, Riaz Brette, Eddy Dae*, Elaine Round, Fredry Hellen and Sarah Baxter-Wright

Introduction: The impact of e-liquid flavor on nicotine uptake is an important area of consideration regarding biological uptake of nicotine with conflicting data. This paper reports on Pharmaco Kinetics (PK) of plasma nicotine uptake and a subjective measure of Overall Product Liking (OPL) using four different e-liquid flavors in two commercially available cartridge-based Electronic Nicotine Delivery System (ENDS) systems, Vuse Vibe and Vuse Ciro.

Aims and methods: Two single-center, open-label, parallel cohort confinement studies were conducted in 2017. In total, 287 eligible adult cigarette smokers and dual users of ENDS were enrolled and randomized to Vuse Vibe (3% nicotine content by weight) in four flavors (Original (n=36), Mint (n=36), Tropical (n=36), or Nectar (n=36)), or to Vuse Ciro (1.5% nicotine content by weight) in four flavors (Original (n=35), Mint (n=36), Melon (n=39), or Tropical (n=33)). Subjects used their assigned products ad libitum during a 10-minute session after 12 hours of nicotine abstinence, and plasma nicotine PK and OPL were evaluated.

Results: Across each ENDS platform, baseline-adjusted geometric mean C_max values for the four evaluated flavors were generally similar. C_max values ranged from 4.60 to 6.84 ng/mL for Vuse Vibe and 4.35 to 5.88 ng/mL for Vuse Ciro among four flavor variants of each ENDS. While the study was not designed to compare nicotine uptake across products, nicotine uptake based on baseline adjusted C_max and AUC_nic0-60 was generally higher in the Vuse Vibe group compared to the Vuse Ciro group, reflective of differences in nicotine concentration. OPL scores ranged from 6.1 to 7.3 for the Vuse Vibe group and 5.8 to 7.2 for the Vuse Ciro group.

Conclusion: Nicotine uptake for two different ENDS product platforms was similar across a range of assessed e-liquid flavors as evidenced by overlap of 95% confidence intervals in C_max and AUC_{nic 0-60.}

Implications: In these two studies on PK assessments of e-liquids containing 1.5 and 3.0% nicotine-salt in ENDS devices, we found similar (overlap of 95% confidence intervals) nicotine uptake profiles in subjects with different peak plasma concentrations between the two ENDS platforms that were mirrored by the difference in nicotine content