Estimating human pharmacokinetic parameters for electronic nicotine delivery system products from chemical analyses of their aerosols

Abstract

AbstractThe ability of Electronic Nicotine Delivery Systems (ENDS) to deliver nicotine is central to their function to substitute for cigarettes, allowing people who smoke to switch away from smoking, thus reducing their exposure to harmful chemicals in cigarette smoke. The nicotine concentration in ENDS e‐liquid has proved to be a poor predictor of nicotine uptake in users. Using meta‐analytic methods to analyze 12 pharmacokinetic studies of nicotine‐salt closed‐system ENDS, this paper examines whether the mass of nicotine/puff of aerosol can predict Cmax in pharmacokinetic studies. Cmax values were available for 38 products, in 58 use conditions (including both controlled [3 s] and ad libitum puffing), comprising 1769 participant observations. Nicotine/puff data reflected chemical analyses of aerosol obtained under nonintense (3 s) or intense (6 s) machine puffing. Meta‐regression analyses (weighted by reliability of Cmax estimate) assessed the relationship of nicotine/puff to Cmax. In some models, empirical data were used to impute the variation in Cmax or the nicotine/puff value under intense puffing. In simple linear models, Cmax was significantly associated with nicotine/puff under all combinations of intense/nonintense and controlled/ad‐libitum conditions, with R2 values of 0.71–0.77. More complex models based on quadratic effects or log[nicotine/puff] did not generally improve upon more parsimonious linear models. Application of the model illustrates the divergence between nicotine concentration in e‐liquids and expected Cmax when other ENDS parameters vary. The meta‐analytic model may have utility in settings where clinical pharmacokinetic data are not available, including product development.