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CORESTA Congress, Kunming, 2018, Smoke Science/Product Technology Groups, STPOST 05

Examining intra-individual and inter-individual variability of plasma nicotine PK parameters in e-vapor use by adult cigarette smokers in three studies

LIANG Qiwei; ZHAO Yuxi; WANG Jingzhu; BLACK R.
Altria Client Services LLC, Center for Research and Technology, Richmond, VA, U.S.A.

Pharmacokinetic studies are often used to assess the rate and amount of nicotine delivery into the bloodstream during product use. Knowledge about intra-individual and inter-individual variability of pharmacokinetic (PK) parameters is important in the design of PK study for e vapor products (EVPs). We analyzed two plasma nicotine PK parameters, maximum concentration (Cmax) and area under the curve (AUC) from three randomized controlled crossover PK studies (n = 27, 36, 38, respectively) in which various commercial and prototype EVPs were used by adult cigarette smokers under two different use conditions. The first condition was a controlled use of 10 inhalations of 4 second duration with 30 second intervals and the second condition was an ad libitum use condition (use for 10 minutes without restrictions on inhalation times and duration). A linear mixed model that included study product, sequence and period as fixed effect and subject as random effect was used to estimate the intra- and inter-individual variability. The average variability (CV %) across the three studies was larger under the ad libitum condition (intra-individual mean = 32.3 % and inter-individual mean = 52.9 % for Cmax; intra-individual mean = 26.3 % and inter-individual mean = 54.3 % for AUC) than under the controlled condition (intra-individual mean = 31.6 % and inter-individual mean = 39.3 % for Cmax; intra-individual mean = 22.8 % and inter-individual mean = 36.2 % for AUC). The average intra-individual variability across the three studies for Cmax and AUC was smaller than the average inter-individual variability under both conditions. In each study, the intra-individual variability for both parameters was smaller than the inter-individual variability. For the ad libitum condition, the inter-individual CV in Cmax was 52 %, 52 % and 53 %, respectively in three studies and the inter-individual CV was all around 54 % for AUC in three studies, indicating consistency across studies. These variability estimates can inform design of future EVP PK studies.