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Drug pharmacokinetics determined by real-time analysis of mouse breath
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Li, Xue, Martinez-Lozano Sinues, Pablo, Dallmann, Robert, Bregy, Lukas, Hollmén, Maija, Proulx, Steven, Brown, Steven A., Detmar, Michael, Kohler, Malcolm and Zenobi, Renato (2015) Drug pharmacokinetics determined by real-time analysis of mouse breath. Angewandte Chemie International Edition, Volume 54 (Number 27). pp. 7815-7818. doi:10.1002/anie.201503312 ISSN 1433-7851.
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Official URL: http://dx.doi.org/10.1002/anie.201503312
Abstract
Noninvasive, real-time pharmacokinetic (PK) monitoring of ketamine, propofol, and valproic acid, and their metabolites was achieved in mice, using secondary electrospray ionization and high-resolution mass spectrometry. The PK profile of a drug influences its efficacy and toxicity because it determines exposure time and levels. The antidepressant and anaesthetic ketamine (Ket) and four Ket metabolites were studied in detail and their PK was simultaneously determined following application of different sub-anaesthetic doses of Ket. Bioavailability after oral administration vs. intraperitoneal injection was also investigated. In contrast to conventional studies that require many animals to be sacrificed even for low-resolution PK curves, this novel approach yields real-time PK curves with a hitherto unmatched time resolution (10 s), and none of the animals has to be sacrificed. This thus represents a major step forward not only in animal welfare, but also major cost and time savings.
Item Type: | Journal Article | ||||||||
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Subjects: | R Medicine > RM Therapeutics. Pharmacology | ||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Pharmacokinetics, Breath tests, Drugs -- Metabolism | ||||||||
Journal or Publication Title: | Angewandte Chemie International Edition | ||||||||
Publisher: | Wiley | ||||||||
ISSN: | 1433-7851 | ||||||||
Official Date: | 26 June 2015 | ||||||||
Dates: |
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Volume: | Volume 54 | ||||||||
Number: | Number 27 | ||||||||
Number of Pages: | 4 | ||||||||
Page Range: | pp. 7815-7818 | ||||||||
DOI: | 10.1002/anie.201503312 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Restricted or Subscription Access |
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