Randomized studies assessing the effect of flavor on pharmacokinetic and subjective parameters for dry and moist nicotine pouches.

Abstract

Nicotine pouches (NPs) have different formulations (e.g., dry or moist), and the vast majority are flavored. However, it is unclear if flavors exert any effect on nicotine pharmacology and subjective parameters. Data from two, open-label, randomized, nine-way cross-over, single-dose administration, pharmacokinetic and subjective effects studies were analyzed, evaluating dry 6-mg and moist 9-mg NPs, respectively. The studies included unflavored and flavored varieties (flavor characteristics: traditional [tobacco], cooling, minty, fruit, beverage). All participants were adults who currently used snus and/or NPs daily (n = 38 for moist, n = 39 for dry). Maximum plasma concentrations (C_max) of nicotine were observed at NP removal at ~60min (T_max), with overlapping geometric least squares mean (GLSM) values for the dry and moist products (12.08-15.07ng/mL). The total nicotine exposure (calculated as area under the curve from time point 0 to infinity, AUC_inf) was 40.84-50.86h⁎ng/mL, with overlapping GLSM values for dry and moist varieties. Equivalence testing for AUC_inf and C_max between unflavored and flavored varieties showed equivalence for all varieties except two of the moist minty NPs. For subjective parameters, the effect of flavor was more pronounced for moist NPs, with participants rating the flavored varieties higher for satisfaction, product liking, and intent to use again. For dry varieties, flavor had no effect on C_max and AUC_inf, but two moist varieties were different from moist unflavored. Flavor did not affect T_max for dry or moist NPs. Considerable variation in participant preferences suggest a need for diverse varieties and product types.