title: Nicotine delivery, retention and pharmacokinetics from various electronic cigarettes.
abstract: OBJECTIVE
  To measure the systemic retention of nicotine, propylene glycol (PG) and vegetable glycerin (VG) in electronic cigarette (e-cigarette) users, and assess the abuse liability of e-cigarettes by characterizing nicotine pharmacokinetics.
  
  
  METHODS
  E-cigarette users recruited over the internet participated in a 1-day research ward study. Subjects took 15 puffs from their usual brand of e-cigarette. Exhaled breath was trapped in gas-washing bottles and blood was sampled before and several times after use.
  
  
  METHODS
  San Francisco, California, USA.
  
  
  METHODS
  Thirteen healthy, experienced adult e-cigarette users (six females and seven males).
  
  
  METHODS
  Plasma nicotine was analyzed by gas chromatography-mass spectrometry (GC-MS/MS) and nicotine, VG and PG in e-liquids and gas traps were analyzed by LC-MS/MS. Heart rate changes and subjective effects were assessed.
  
  
  RESULTS
  E-cigarettes delivered an average of 1.33 (0.87-1.79) mg [mean and 95% confidence interval (CI)] of nicotine, and 93.8% of the inhaled dose, 1.22 (0.80-1.66) was systemically retained. Average maximum plasma nicotine concentration (Cmax ) was 8.4 (5.4-11.5) ng/ml and time of maximal concentration (Tmax ) was 2-5 minutes. One participant had Tmax of 30 minutes. 84.4% and 91.7% of VG and PG, respectively, was systemically retained. Heart rate increased by an average of 8.0 beats per minute after 5 minutes. Withdrawal and urge to smoke decreased and the e-cigarettes were described as satisfying.
  
  
  CONCLUSIONS
  E-cigarettes can deliver levels of nicotine that are comparable to or higher than typical tobacco cigarettes, with similar systemic retention. Although the average maximum plasma nicotine concentration in experienced e-cigarette users appears to be generally lower than what has been reported from tobacco cigarette use, the shape of the pharmacokinetic curve is similar, suggesting addictive potential.
authors.affiliation: Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, University of California, San Francisco, CA, USA.|Center for Tobacco Control Research and Education, University of California, San Francisco, CA, USA.|Tobacco Center of Regulatory Science, University of California, San Francisco, CA, USA.
authors.forename: Gideon
authors.initials: G
authors.lastname: St Helen
authors.affiliation: Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Havel
authors.affiliation: Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Delia A
authors.initials: DA
authors.lastname: Dempsey
authors.affiliation: Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, University of California, San Francisco, CA, USA.|Center for Tobacco Control Research and Education, University of California, San Francisco, CA, USA.|Tobacco Center of Regulatory Science, University of California, San Francisco, CA, USA.
authors.forename: Peyton
authors.initials: P
authors.lastname: Jacob
authors.affiliation: Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, University of California, San Francisco, CA, USA.|Center for Tobacco Control Research and Education, University of California, San Francisco, CA, USA.|Tobacco Center of Regulatory Science, University of California, San Francisco, CA, USA.|Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
authors.forename: Neal L
authors.initials: NL
authors.lastname: Benowitz
mesh_terms: D000328:Adult; D001944:Breath Tests; D002853:Chromatography, Liquid; D066300:Electronic Nicotine Delivery Systems; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005990:Glycerol / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D018722:Nicotinic Agonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019946:Propylene Glycol / Q000008:administration & dosage* / Q000378:metabolism; D012997:Solvents / Q000008:administration & dosage* / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D018722:Nicotinic Agonists; D012997:Solvents; D019946:Propylene Glycol; D009538:Nicotine; D005990:Glycerol
keywords: Abuse liability; addiction; e-cigarette; nicotine pharmacokinetics; nicotine retention; propylene glycol; vegetable glycerin