Pharmacokinetics of nicotine following the controlled use of a prototype novel tobacco vapor product

Abstract

The objective of this clinical study was to investigate the pharmacokinetics of nicotine following the use of a prototype novel tobacco vapor (PNTV) product in comparison to a conventional cigarette (CC1). The study was conducted in Japanese healthy adult male smokers, using an open-label, randomized, two-period crossover design, to assess the pharmacokinetics of nicotine after controlled use of a PNTV product or CC1. During the study period, blood samples were drawn from subjects for the measurement of plasma nicotine concentrations and nicotine intake was estimated from the mouth level exposure (MLE). The C_max and AUC_last following the use of PNTV product were 45.7% and 68.3%, respectively, of those obtained with CC1 and there were no significant differences in the tmax and t_1/2 between PNTV product and CC1. The estimated MLE following the use of PNTV product was approximately two-thirds of that obtained following the smoking of CC1, but the relative bioavailability of PNTV product to CC1 was approximately 104%. The differences in C_max and AUC_last between PNTV product and CC1 therefore are explained by differences in nicotine intake. These results suggest that the PNTV product shows a similar pharmacokinetic profile to CC1, while delivering less nicotine following controlled use.

Keywords: Clinical study; Japanese healthy adult male smokers; Mouth level exposure; Nicotine; Pharmacokinetics; Prototype novel tobacco vapor product; Relative bioavailability.