A comprehensive physiologically based pharmacokinetic (PBPK) model for nicotine in humans from using nicotine-containing products with different routes of exposure
Open Access
- 20 January 2022
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 12 (1), 1-18
- https://doi.org/10.1038/s41598-022-05108-y
Abstract
Physiologically based pharmacokinetic (PBPK) modeling can be a useful tool for characterizing nicotine pharmacokinetics (PK) from use of tobacco products. We expand a previously published PBPK model to simulate a nicotine PK profile, following single or multiple use of various tobacco products [cigarettes, smokeless tobacco, and electronic nicotine delivery systems, or a nicotine inhaler (NICOTROL)] The uptake route in the model was designed to allow for three uptake compartments: buccal cavity (BC), upper respiratory tract (URT) (conducting and transitional airways) and lower respiratory tract (alveolar region). Within each region, the model includes product-specific descriptions of the flux of nicotine into plasma, as well as the flux of nicotine from the BC and URT to the gastrointestinal tract. These descriptions are based on regional deposition and diffusion models of nicotine into plasma, which depends on the product type. Regional deposition flux combined with regional differences in physiological parameters (e.g., blood perfusion ratio and tissue thickness) play a key role in the product-specific PK profile of nicotine. The current model describes the slower flux of nicotine into plasma across the BC and URT, as well as the rapid flux known to occur in the alveolar region. Overall, the addition of the BC and respiratory tract compartments to the nicotine model provided simulation results that are comparable to the nicotine time-course plasma concentrations reported from clinical studies for the four product categories simulated.This publication has 35 references indexed in Scilit:
- Determination of Nicotine Absorption from Multiple Tobacco Products and Nicotine GumNicotine & Tobacco Research, 2012
- Derivation of Mass Transfer Coefficients for Transient Uptake and Tissue Disposition of Soluble and Reactive Vapors in Lung AirwaysAnnals of Biomedical Engineering, 2011
- Human Blood Concentrations of Cotinine, a Biomonitoring Marker for Tobacco Smoke, Extrapolated from Nicotine Metabolism in Rats and Humans and Physiologically Based Pharmacokinetic ModelingInternational Journal of Environmental Research and Public Health, 2010
- GNU MCSim: Bayesian statistical inference for SBML-coded systems biology modelsBioinformatics, 2009
- In vivo human buccal permeability of nicotineInternational Journal of Pharmaceutics, 2006
- The Effect of Tobacco Blend Additives on the Retention of Nicotine and Solanesol in the Human Respiratory Tract and on Subsequent Plasma Nicotine Concentrations during Cigarette SmokingChemical Research in Toxicology, 2004
- The Nicotine InhalerClinical Pharmacokinetics, 2001
- A physiologically based pharmacokinetic model for nicotine and cotinine in manJournal of Pharmacokinetics and Biopharmaceutics, 1992
- Absorption of Nicotine from a Cigarette That Does Not Burn TobaccoPharmacology, 1988
- A NEW AGE FOR SNUFF?The Lancet, 1980