title: Nicotine and cotinine exposure from electronic cigarettes: a population approach.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, West Walnut Street, Indianapolis, IN, 46202, USA, nvelezde@iu.edu.
authors.forename: Nieves
authors.initials: N
authors.lastname: Vélez de Mendizábal
authors.forename: David R
authors.initials: DR
authors.lastname: Jones
authors.forename: Andy
authors.initials: A
authors.lastname: Jahn
authors.forename: Robert R
authors.initials: RR
authors.lastname: Bies
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Brown
mesh_terms: D000293:Adolescent; D000328:Adult; D001944:Breath Tests / Q000379:methods; D002248:Carbon Monoxide / Q000032:analysis; D003367:Cotinine / Q000097:blood* / Q000493:pharmacokinetics; D066300:Electronic Nicotine Delivery Systems; D005260:Female; D006801:Humans; D019570:Inhalation Exposure; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D009538:Nicotine / Q000097:blood* / Q000493:pharmacokinetics; D012907:Smoking / Q000097:blood; D012984:Software; D055815:Young Adult
chemical_list: D009538:Nicotine; D002248:Carbon Monoxide; D003367:Cotinine