A Randomized Crossover Clinical Study to Assess the Effect of Oral Nicotine Pouches Used for Different Durations on Plasma Nicotine Pharmacokinetics in Healthy Oral Pouch Consumers.

Oral nicotine pouches (NPs), although addictive and not risk-free, have potential application for a tobacco harm reduction approach. This study aims to further characterize their ability to deliver nicotine effectively. This randomized seven-way crossover PK study in healthy oral pouch consumers evaluated 11 and 20 mg NPs used for 10, 20, and 30 min, and for 30 min with expulsion of saliva. Used pouches were analyzed for extracted nicotine, flavor components, and sweeteners. The Cmax and AUC0-4 h increased with nicotine strength and usage time (18.9-21.6 and 26.7-33.6 ng/mL; 24.6-43.0 and 36.4 to 65.6 h ng/mL for the 11 and 20 mg NPs, respectively). Extracted nicotine was greater for the 11-mg than for the 20-mg NP, (10 min, 28.0% vs. 22.4%; 20 min, 35.8% vs. 29.6%; 30 min, 43.7% vs. 36.9%, respectively). Only 1.8% of the nicotine measured in the reference NPs was detected in saliva collected over the 30 min use period. Use of 20-mg NP for 30 min resulted in the extraction of 30.1% flavor components and 17.3% sweeteners, but only 0.16% and 3.4% of the amount measured in the reference NPs were detected in saliva, respectively. Thus, very little nicotine, flavor components, and sweeteners were swallowed during NP use. This study shows NPs can deliver nicotine effectively to satisfy smokers' nicotine desire. Nicotine delivery to the consumer increases with the duration of use. Our findings suggest that smokers who switch completely to an NP can obtain their accustomed amount of nicotine during normal product use. International Standard Registered Clinical Trial number: ISRCTN12265853.