Simulation of electronic nicotine delivery systems (ENDS) aerosol dosimetry and nicotine pharmacokinetics

IF 3.1 Q2 TOXICOLOGY
Jeffry Schroeter , Bahman Asgharian , Owen Price , Aaron Parks , Darren Oldson , Jonathan Fallica , Gladys Erives , Cissy Li , Olga Rass , Arit Harvanko , Kamau Peters , Susan Chemerynski
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引用次数: 0

Abstract

Electronic nicotine delivery systems (ENDS) heat a liquid solution typically containing propylene glycol, vegetable glycerin, water, nicotine, and flavor chemicals to deliver an aerosol to the user. ENDS aerosols are complex, multi-constituent mixtures of droplets and vapors. Lung dosimetry predictions require mechanistic models that account for the physico-chemical properties of the constituents and thermodynamic processes of the aerosol as it travels through the respiratory tract and deposits in lung airways. In this study, a model formulated to predict ENDS aerosol deposition in the oral cavity and lung airways was linked with a physiologically-based pharmacokinetic (PBPK) model to predict nicotine pharmacokinetics (PK) as a function of product characteristics and puff topography. Predicted plasma nicotine PK compared favorably with available experimental data and captured the rapid increase in plasma levels followed by a clearance phase after ENDS use. E-liquid nicotine concentration and puff duration substantially increased nicotine lung deposition and plasma nicotine levels. Increasing the puff duration from 1 to 5 s while assuming a constant aerosol flow rate resulted in an ∼5-fold increase in nicotine lung deposition (45.0 µg to 243.7 µg) and increased maximum plasma nicotine concentrations from 4.7 ng/mL to 25.0 ng/mL; increasing the e-liquid nicotine concentration from 1 % to 5 % yielded increases in nicotine lung deposition (41.0 µg to 204.5 µg) and maximum plasma nicotine concentration (4.2 ng/mL to 21.1 ng/mL). Model predictions demonstrate the sensitivity of ENDS aerosol lung deposition and plasma nicotine profiles to user behavior and allow for quantification of constituent deposition and nicotine absorption after ENDS use.

模拟电子尼古丁输送系统(ENDS)的气溶胶剂量测定和尼古丁药代动力学
电子尼古丁给药系统(ENDS)加热通常含有丙二醇、植物甘油、水、尼古丁和香料化学品的液体溶液,向用户提供气溶胶。ENDS气溶胶是由液滴和蒸汽组成的复杂、多成分混合物。肺部剂量测定预测需要机理模型,以说明气溶胶通过呼吸道并沉积在肺部呼吸道时各成分的物理化学特性和热力学过程。在这项研究中,为预测ENDS气溶胶在口腔和肺部气道的沉积而建立的模型与基于生理学的药代动力学(PBPK)模型相结合,预测了尼古丁药代动力学(PK)与产品特性和吹气地形的关系。预测的血浆尼古丁药代动力学与现有的实验数据相比效果良好,并捕捉到了使用 ENDS 后血浆水平迅速上升并随之进入清除阶段的现象。电子烟尼古丁浓度和吸食时间大大增加了尼古丁的肺沉积和血浆尼古丁水平。在假定气溶胶流速不变的情况下,将吸食时间从1秒增加到5秒,尼古丁肺沉积量增加了5倍(从45.0微克增加到243.7微克),最大血浆尼古丁浓度从4.7纳克/毫升增加到25.0纳克/毫升;电子液体尼古丁浓度从1%增加到5%,尼古丁肺沉积量(41.0微克增加到204.5微克)和最大血浆尼古丁浓度(4.2纳克/毫升增加到21.1纳克/毫升)也随之增加。模型预测证明了ENDS气溶胶肺沉积和血浆尼古丁曲线对使用者行为的敏感性,并允许对ENDS使用后的成分沉积和尼古丁吸收进行量化。
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来源期刊
Computational Toxicology
Computational Toxicology Computer Science-Computer Science Applications
CiteScore
5.50
自引率
0.00%
发文量
53
审稿时长
56 days
期刊介绍: Computational Toxicology is an international journal publishing computational approaches that assist in the toxicological evaluation of new and existing chemical substances assisting in their safety assessment. -All effects relating to human health and environmental toxicity and fate -Prediction of toxicity, metabolism, fate and physico-chemical properties -The development of models from read-across, (Q)SARs, PBPK, QIVIVE, Multi-Scale Models -Big Data in toxicology: integration, management, analysis -Implementation of models through AOPs, IATA, TTC -Regulatory acceptance of models: evaluation, verification and validation -From metals, to small organic molecules to nanoparticles -Pharmaceuticals, pesticides, foods, cosmetics, fine chemicals -Bringing together the views of industry, regulators, academia, NGOs
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