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

• Published in: Drug and alcohol dependence 2017-09, Vol.178, p.391-398
• Main Authors: St.Helen, Gideon, Dempsey, Delia A., Havel, Christopher M., Jacob, Peyton, Benowitz, Neal L.
• Format: Article
• Language: English
• Subjects: Absorption; Blood; Cigarettes; Cross-Over Studies; E-cigarette pharmacology; E-cigarettes; Electronic cigarettes; Electronic Nicotine Delivery Systems; Exposure; Females; Flavor; Flavoring Agents - pharmacology; Flavors; Heart rate; Heart Rate - drug effects; Hospitalization; Humans; Hydrogen ions; Liking; Liquids; Males; Nicotine; Nicotine - pharmacology; Nicotine delivery; Nicotine pharmacokinetics; pH effects; Pharmacology; Smoking; Taste - drug effects; Titration; Tobacco; Tobacco Products
• ISSN: 0376-8716; 1879-0046
• DOI: 10.1016/j.drugalcdep.2017.05.042

•Rate of nicotine absorption was different between strawberry and tobacco e-liquids.•The pH of e-liquids may influence rate of nicotine absorption.•Vapers titrate their nicotine exposure but extent of titration varies with flavor. To describe the effect of e-liquid flavors on nicotine intake and pharmacology of e-cigarettes. 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. 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, Cmax 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. 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.