Objectives • To compare in vivo extracted dose and pharmacokinetics of nicotine from ZYN® with Swedish snus (General) and U.S moist snuff (Longhorn) • To evaluate the effect of the flavor component methyl salicylate on nicotine extraction and uptake Methods Three clinical studies were conducted as open randomized multiple-way cross-over trials. The treatments were administered as single doses during 60 minutes. Blood levels of nicotine were followed over 6 hours after administration. Results The extraction of nicotine in the ZYN® products were approx. 50-60 %, compared to ca 30 % and 20 % in Swedish snus and U.S. moist snuff, respectively. The peak plasma concentrations (Cmax) of ZYN® (6 mg/unit), Longhorn (18 mg/unit), ZYN (8 mg/unit) and General (16 mg/unit) were approx. 14, 17, 18 and 21 ng/ml. Conclusion The higher rate of extraction for the ZYN® pouch could be explained by the different geometry, which would lead to a more efficient saliva penetration of the pouch. The evaluation of pharmacokinetics showed that, the ZYN® products gave rise to significantly larger nicotine uptake than conventional, tobacco-based products with equivalent nicotine content. However, more important, the studies also showed that the ZYN® products do not entail a higher nicotine exposure compared with some commercially available tobacco-based snus or moist snuff products that are currently common on the Scandinavian and U.S. markets. The assessment of the effect of methyl salicylate on nicotine extraction and plasma concentrations showed no significant difference for neither ZYN® or tobacco-based moist snuff products.