A randomised study to assess the nicotine pharmacokinetics of an oral nicotine pouch and two nicotine replacement therapy products

Nicotine replacement therapies (NRTs) are intended for short-term use to help cigarette smokers to quit. Some smokers find NRTs ineffective or seek a more satisfactory source of nicotine. Tobacco-free oral nicotine pouch (NP) products have emerged as a potential reduced risk product compared with cigarettes and other tobacco products. In a randomised crossover clinical study, thirty-four healthy adult smokers were enrolled and their nicotine C(max) and AUC(0-T) determined for three 4 mg nicotine products (NP, gum, lozenge) under fasting conditions. The NP, lozenge and gum mean C(max) values were 8.5, 8.3 and 4.4 ng/mL, AUC(0-T) values were 30.6, 31.5 and 14.3 ng*h/mL, respectively. The NP showed similar nicotine bioavailability to the lozenge (p = 0.6526 (C(max)), p = 1.0000 (AUC(0-T))), and superior bioavailability to the gum (p < 0.0001 for C(max) and AUC(0-T)). Compared with the lozenge, the NP demonstrated greater product satisfaction with a higher number of positive responses to subjective satisfaction questions. All products were judged to be well-tolerated; the incidence of minor adverse events was lower for the NP (18.2%) than the lozenge (33.3%) or gum (18.8%). In summary, NPs may provide smokers with a more satisfying alternative nicotine source as compared to the reference NRTs. Study Registry/Registered Trial No: ISRCTN/ISRCTN65708311.