Nicotine pouch pharmacokinetics compared to smoked tobacco: A systematic review and meta-analysis

Nicotine pouches (NP) are novel agents that deliver nicotine through buccal absorption as opposed to combustion. They are proposed as a harm reduction tool compared to smoking tobacco. However, there is limited evidence on their efficacy and safety. This review article summarizes the current evidence regarding NP pharmacokinetics compared to conventional tobacco products. We searched Medline, Embase, CENTRAL and Scopus for studies that assessed pharmacokinetic parameters of nicotine pouches. We identified studies involving tobacco-dependent adults and examined pharmacokinetic parameters such as total exposure, peak concentration, and time to peak. A meta-analysis was conducted using random-effects models to calculate pooled effect sizes. The Cochrane ROB 2.0 tool was used to evaluate the risk of bias in the included studies. A total of seven RCTs and crossover trials were included. Five compared NP pharmacokinetics with smoked tobacco, while two used moist snuff as comparators. Total nicotine exposure was significantly lower with 1.5 mg and 2 mg pouches, similar with 3.5 mg and 4 mg pouches, and significantly higher with pouches containing 8 mg or more when compared to cigarettes. A meta-analysis of three trials showed that 4 mg pouches delivered 91.73 % (95 % CI 85.03 %-98.42 %) of cigarette total nicotine exposure. Peak concentration was significantly lower with 1.5 mg, 2 mg, and 3.5 mg pouches while higher concentration pouches had greater peak when compared to cigarettes. A meta-analysis of three trials showed that 4 mg pouches showed a peak nicotine concentration of 69.15 % (95 % CI 58.55 %-79.76 %) compared with cigarettes. Peak nicotine concentration was consistently achieved earlier with cigarettes (5-8 min) than with pouches (20-65 min). Despite their buccal absorption, 4 mg pouches (most commonly used), deliver similar total nicotine exposure to cigarettes, though with lower peak concentrations and slower absorption. When combined with their flavours and aggressive marketing to youth, this raises concerns about the potential of nicotine pouches to cause nicotine dependence, especially among those using the product recreationally.