Vélez de Mendizábal Nieves, Jones David R, Jahn Andy, Bies Robert R, Brown Joshua W
Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, West Walnut Street, Indianapolis, IN, 46202, USA,
Clin Pharmacokinet. 2015 Jun;54(6):615-26. doi: 10.1007/s40262-014-0221-7.
Electronic cigarettes (e-cigarettes) are a recent technology that has gained rapid acceptance. Still, little is known about them in terms of safety and effectiveness. A basic question is how effectively they deliver nicotine; however, the literature is surprisingly unclear on this point. Here, a population pharmacokinetic model was developed for nicotine and its major metabolite cotinine with the aim to provide a reliable framework for the simulation of nicotine and cotinine concentrations over time, based solely on inhalation airflow recordings and individual covariates [i.e., weight and breath carbon monoxide (CO) levels].
This study included ten adults self-identified as heavy smokers (at least one pack of cigarettes per day). Plasma nicotine and cotinine concentrations were measured at regular 10-min intervals for 90 min while human subjects inhaled nicotine vapor from a modified e-cigarette. Airflow measurements were recorded every 200 ms throughout the session. A population pharmacokinetic model for nicotine and cotinine was developed based on previously published pharmacokinetic parameters and the airflow recordings. All of the analyses were performed with the non-linear mixed-effect modeling software NONMEM(®) version 7.2.
The results show that e-cigarettes deliver nicotine effectively, although the pharmacokinetic profiles are lower than those achieved with regular cigarettes. Our pharmacokinetic model effectively predicts plasma nicotine and cotinine concentrations from the inhalation volume, and initial breath CO.
E-cigarettes are effective at delivering nicotine. This new pharmacokinetic model of e-cigarette usage might be used for pharmacodynamic analysis where the pharmacokinetic profiles are not available.
电子烟是一项近期迅速获得认可的技术。然而，关于其安全性和有效性，人们所知甚少。一个基本问题是它们输送尼古丁的效果如何；然而，文献在这一点上出人意料地不明确。在此，我们为尼古丁及其主要代谢物可替宁建立了群体药代动力学模型，目的是仅基于吸入气流记录和个体协变量（即体重和呼出一氧化碳（CO）水平），提供一个可靠的框架来模拟尼古丁和可替宁浓度随时间的变化。
本研究纳入了10名自认为是重度吸烟者（每天至少一包香烟）的成年人。在人类受试者从改良电子烟吸入尼古丁蒸汽的90分钟内，每隔10分钟定期测量血浆尼古丁和可替宁浓度。在整个过程中，每200毫秒记录一次气流测量值。基于先前发表的药代动力学参数和气流记录，建立了尼古丁和可替宁的群体药代动力学模型。所有分析均使用非线性混合效应建模软件NONMEM® 7.2版进行。
结果表明，电子烟能有效输送尼古丁，尽管其药代动力学特征低于普通香烟。我们的药代动力学模型能根据吸入量和初始呼出CO有效预测血浆尼古丁和可替宁浓度。
电子烟在输送尼古丁方面是有效的。这种新的电子烟使用药代动力学模型可用于在无法获得药代动力学特征时的药效学分析。
