The effect of cut sizes and pH of tobacco leaf in smokeless tobacco products on the pharmacokinetics of nicotine

The absorption of nicotine from smokeless tobacco products (STPs) in humans is affected by various factors, including nicotine content, flavoring compounds, cutting format, tobacco cut sizes, and pH. In this study, participants were asked to use STP 1 for a specific period, after which the nicotine content was measured before and after use to determine the release rate using the Weibull model. Blood samples were collected from participants after 30 min of using STP 1 to assess nicotine pharmacokinetics. Additionally, guinea pigs were administered four types of STPs with varying pH levels, and tobacco cut sizes, but with identical nicotine content on the oral mucosa to evaluate nicotine pharmacokinetics. The human results showed that nicotine in STP was quickly released in the mouth, reaching 73.66% within 30 min. Plasma nicotine concentration in guinea pigs and human participants were comparable following STP use. Guinea pigs exposed to STPs with smaller tobacco cut sizes or higher pH absorbed more nicotine and metabolized it more slowly. The findings suggest that pH and cut size of STPs are key factors affecting nicotine absorption, while the impact of flavoring agents and other components on nicotine absorption remains to be determined.