Drug Pharmacokinetics Determined by Real-Time Analysis of Mouse Breath

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Author(s) Li, Xue, Sinues, Pablo M.-L., Dallmann, Robert, Bregy, Lukas, Hollmén, Maija, Proulx, Steven, Brown, Steven A., Detmar, Michael, Kohler, Malcolm, Zenobi, Renato
Publication Type Journal Items, Publication Status: Published
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Title Drug Pharmacokinetics Determined by Real-Time Analysis of Mouse Breath
Author(s) Li, Xue
Sinues, Pablo M.-L.
Dallmann, Robert
Bregy, Lukas
Hollmén, Maija
Proulx, Steven
Brown, Steven A.
Detmar, Michael
Kohler, Malcolm
Zenobi, Renato
Journal or Series Title Angewandte Chemie. International Edition in English
Volume Number 54
Issue Number 27
Start Page 7815
End Page 7818
ISSN 1433-7851
0570-0833
1521-3773
Publisher Wiley
Publication Place Weinheim
Publication Date 2015-06-26
Keyword(s) Breath analysis
High-resolution mass spectrometry
Ketamine
Pharmacokinetics
Secondary electrospray ionization
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 (10s), 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.
DOI 10.1002/anie.201503312
Additional Notes Published online 27 May 2015
Document Type Article
Publication Status Published
Language English
Assigned Organisational Unit(s) 03430
03683
Organisational Unit(s)
NEBIS System Number 000033716
Source Database ID WOS-000356886600012
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@article{L2015,
  author = "Li, Xue and Sinues, Pablo M.-L. and Dallmann, Robert and Bregy, Lukas and Hollm{\'{e}}n, Maija and Proulx, Steven and Brown, Steven A. and Detmar, Michael and Kohler, Malcolm and Zenobi, Renato",
  title = "{D}rug {P}harmacokinetics {D}etermined by {R}eal-{T}ime {A}nalysis of {M}ouse {B}reath",
  journal = "Angewandte Chemie. International Edition in English",
  year = 2015,
  volume = "54",
  number = "27",
  pages = "7815--7818",
  month = jun,
}


E-Citations record created: Mon, 27 Jul 2015, 10:06:53 CET