However, a small study of loose and pouched snus users had previously indicated that the average systemic uptake of nicotine for these groups (based on nicotine equivalents in 24 hr urine), were comparable (Andersson, Bjornberg, & Curvall, 1994) despite Vorinostat molecular weight a higher average level of daily consumption of tobacco by loose snus users compared with pouched. The loose and pouched product types in the study had comparable nicotine content, suggesting that differences in levels of nicotine extraction and/or bioavailability between the two forms of snus might account for the relatively higher proportion of nicotine uptake measured for pouched snus users. Lunell and Lunell (2005) evaluated the extraction of nicotine from snus and measured steady-state plasma nicotine concentrations following repeated use of four Swedish pouched snus products with nicotine content ranging from 4.

53 to 8.84 mg or a 2 mg nicotine gum over the course of 1 day. The amount of nicotine extracted as a percentage of the total nicotine content varied across snus products from 22% to 44%, compared with 44% extraction from the nicotine gum. Overall, the three moist snus samples gave rise to higher steady-state plasma nicotine levels than the dry snus and nicotine gum. In a more recent study, Lunell and Curvall (2011) investigated single-dose pharmacokinetics and subjective effects for two pouched snus products, each containing approximately 8�C10 mg of nicotine per pouch, and a high-dose (4 mg) nicotine chewing gum. They reported faster absorption of nicotine from the snus products, although the Cmax was significantly higher for one snus product compared with the gum.

All products were used for 30 min and there were no significant differences in tmax across products. The study concluded that the relatively rapid rise in plasma nicotine, faster onset of ��head rush��, and reduced urge to smoke in those using snus compared with the nicotine gum could partly explain the common use of snus in Sweden as an aid to quitting smoking. However, significant gaps in knowledge remain. No published nicotine pharmacokinetics study to date has directly compared cigarettes with snus, tested types of snus with varying nicotine content, or compared loose with pouched snus. Therefore, in this study we investigated the effects of snus product form (pouched vs. loose) and nicotine content on nicotine absorption. We also compared these results with a cigarette and a high-dose (4 mg) nicotine chewing gum (an NRT product available over-the-counter [OTC] in Sweden). The study was designed to evaluate nicotine absorption from use of a single product. The protocol of use for the pouched snus and the portion weights of loose snus was based on data from our snus consumption Dacomitinib survey (Digard et al., 2009).