Randomized trials assessing the impact of flavors on pharmacokinetic, pharmacodynamic, and subjective parameters in dry and moist nicotine pouch products

Abstract The nicotine delivery profile of oral nicotine pouches (NPs) affects their abuse liability and ability to function as alternatives for users of riskier combustible products. However, it is unclear if flavors exert any effect on nicotine pharmacology. Here, data from two open-label, randomized, nine-way cross-over, single dose administration pharmacokinetic (PK) and pharmacodynamic (PD) studies of unflavored and flavored varieties of a dry 6 mg nicotine and a moist 9 mg nicotine NP product was analyzed. Maximum plasma concentrations of nicotine (C max ) were observed ~ 1 h after NP administration, with overlapping mean values for the two products (13.02–15.95 ng/mL). The total nicotine exposure (AUC inf ) was 44.65–54.53 h*ng/mL. Equivalence testing for AUC inf and C max between unflavored and flavored NP varieties showed equivalence for all varieties except NP moist D minty and NP moist H minty compared to NP moist A unflavored. Neither AUC inf , C max , or time to maximum nicotine concentration were affected by flavor. The effect of flavor was more pronounced for the moist product, where subjects rated the flavored varieties higher for satisfaction, product-liking, and intent to use again. Overall, large variations were seen between subjects in terms of flavor preferences, highlighting the requirement for multiple varieties and products.