Abstract
The nicotine pharmacokinetics (PK) of non-combustible tobacco and nicotine products, including e-cigarettes, have been extensively studied, with lower or similar nicotine exposure reported for most products compared with combustible cigarettes (CC). We conducted two clinical studies to evaluate nicotine PK and assess nicotine consumption when using two types of e-cigarettes with different flavor variants in U.S. healthy adults who smoke, under similar study protocols.
Study 1 was a randomized, 6-period crossover study conducted in healthy adults who smoke. The primary objective was to evaluate nicotine PK following use of a cig-a-like e-cigarette (eDNC1.0a) with three flavor variants, subjects’ own brand of CC, a nicotine gum, and a reference e-cigarette. Study 2 was a randomized, 7-period crossover study conducted in healthy adults who smoke. The primary objective was to evaluate nicotine PK following use of a closed-tank e-cigarette (eDNC2.0a) with four flavor variants, subjects’ own brand of CC, a nicotine inhaler, and a reference e-cigarette.
In summary, the results of the present studies indicate that nicotine exposure from eDNC1.0a with three flavor variants and eDNC2.0a with four flavor variants was less than that from subjects’ own brand of CC, similar to or less than that from reference e-cigarettes, but similar to or greater than that from pharmaceutical nicotine replacement products. It was observed that the nicotine consumption, estimated based on e-liquid consumption, was generally directly proportional to the level of nicotine exposure as indicated by nicotine PK parameter measurements in each study. Furthermore, linear relationships were found between estimated nicotine consumption and plasma nicotine PK parameters following e-cigarette use. Our findings suggest that mixed effects modelling can be used as a noninvasive method to provide insights of nicotine PK parameters (AUC and Cmax) from e-liquid nicotine consumption data.