Nicotine Delivery to Rats via Lung Alveolar Region-Targeted Aerosol Technology Produces Blood Pharmacokinetics Resembling Human Smoking

Details

• Personal Author:
  Feldman JL ; Liang J ; Shao XM ; Xie X(S) ; Xu B ; Zhu Y
• Description:
  Introduction: Nicotine is a heavily used addictive drug acquired through smoking tobacco. Nicotine in cigarette smoke is deposited and absorbed in the lungs, which results in a rapidly peaked slowly declining arterial concentration. This pattern plays an important role in initiation of nicotine addiction. Methods: A method and device were developed for delivering nicotine to rodents with lung alveolar region-targeted aerosol technology. The dose of delivery can be controlled by the nicotine aerosol concentration and duration of exposure. Results: Our data showed that, in the breathing zone of the nose-only exposure chamber, the aerosol droplet size distribution was within the respirable diameter range. Rats were exposed to nicotine aerosol for 2min. The arterial blood nicotine concentration reached 43.2 +/- 15.7ng/ml (mean +/- SD) within 1-4min and declined over the next 20min, closely resembling the magnitude and early pharmacokinetics of a human smoking a cigarette. The acute inhalation toxicity of nicotine: LC50 = 2.3mg/L was determined; it was affected by pH, suggesting that acidification decreases nicotine absorption and/or bioavailability. Conclusions: A noninvasive method and toolkit were developed for delivering nicotine to rodents that enable rapid delivery of a controllable amount of nicotine into the systemic circulation and brain-inducing dose-dependent pharmacological effects, even a lethal dose. Aerosol inhalation can produce nicotine kinetics in both arterial and venous blood resembling human smoking. This method can be applied to studies of the effects of chronic intermittent nicotine exposure, nicotine addiction, toxicology, tobacco-related diseases, teratogenicity, and for discovery of pharmacological therapeutics. [Description provided by NIOSH]
• Subjects:
  Aerosols Animals Lung Nicotine Occupational Health Respiratory System Safety Smoke Smokers Tobacco Products
• Keywords:
  Animal Studies Lung Function Smoking Tobacco Smoke
• ISSN:
  1462-2203
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  15
• Issue:
  7
• NIOSHTIC Number:
  nn:20055813
• Citation:
  Nicotine Tob Res 2013 Jul; 15(7):1248-1258
• Contact Point Address:
  Xuesi M. Shao, M.D., Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
• Email:
  mshao@ucla.edu
• CAS Registry Number:
  (-)-Nicotine (CAS RN 54-11-5)
• Federal Fiscal Year:
  2013
• Performing Organization:
  University of California Los Angeles
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Nicotine & Tobacco Research
• End Date:
  20270630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:bf63294a3bfd08f21b569d2b85163fcbdc92b2e93dc5fc8fd3e7062385ddcfe2ce518d0c9c98d5ee3c491b122bcb3abbe30b0129506da9204c7677daed22354d
• Download URL:
  https://stacks.cdc.gov/view/cdc/213581/cdc_213581_DS1.pdf
• File Type:
  [PDF - 516.07 KB ]