Gideon St Helen1, Delia A Dempsey2, Christopher M Havel2, Peyton Jacob3, Neal L Benowitz4. 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.
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, 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. 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.
RCT Entities:
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 tobaccoe-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 tobaccoe-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.
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