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Nicotine and Cotinine Exposure from Electronic Cigarettes: A Population Approach

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Abstract

Background and Objectives

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].

Methods

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.

Results

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.

Conclusion

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.

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Acknowledgments

We thank the Disease and Therapeutic Response Modeling Program for the Clinical and Translational Sciences Institute (CTSI) at Indiana University. We thank Karmen Dayhuff and Andrea Meyer for assistance with blood draws, Jeff Sturgeon for designing and implementing the custom electronic cigarette, and Ken Mackie for providing facilities to process the blood plasma. Supported by the Indiana Clinical Translational Sciences Institute, CPAC Core facility grant (JWB, DRJ). Supported by the Indiana Clinical and Translational Sciences Institute, funded in part by grant # RR 02576 from the National Institutes of Health, National Center for Research Resources. Analytical work was performed by the Clinical Pharmacology Analytical Core laboratory, a core laboratory of the Indiana University Melvin and Bren Simon Cancer Center supported by the National Cancer Institute grant P30 CA082709. NVM was supported by Eli Lilly and Company through the Indiana Clinical and Translational Sciences Institute (CTSI).

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Authors and Affiliations

  1. Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, West Walnut Street, Indianapolis, IN, 46202, USA

    Nieves Vélez de Mendizábal & Robert R. Bies

  2. Indiana Clinical and Translational Sciences Institute (CTSI), Indianapolis, IN, USA

    Nieves Vélez de Mendizábal, David R. Jones & Robert R. Bies

  3. Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, 47405, USA

    Andy Jahn & Joshua W. Brown

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  1. Nieves Vélez de Mendizábal
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  2. David R. Jones
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Correspondence to Nieves Vélez de Mendizábal.

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Vélez de Mendizábal, N., Jones, D.R., Jahn, A. et al. Nicotine and Cotinine Exposure from Electronic Cigarettes: A Population Approach. Clin Pharmacokinet 54, 615–626 (2015). https://doi.org/10.1007/s40262-014-0221-7

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  • DOI: https://doi.org/10.1007/s40262-014-0221-7

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