Drug Pharmacokinetics Determined by Real-Time Analysis of Mouse Breath.

Li, Xue; Martinez-Lozano Sinues, Pablo; Dallmann, Robert; Bregy, Lukas; Hollmén, Maija; Proulx, Steven; Brown, Steven A; Detmar, Michael; Kohler, Malcolm; Zenobi, Renato (2015). Drug Pharmacokinetics Determined by Real-Time Analysis of Mouse Breath. Angewandte Chemie (International ed.), 54(27), pp. 7815-7818. Wiley-VCH 10.1002/anie.201503312

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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 (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Proulx, Steven Thomas

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1433-7851

Publisher:

Wiley-VCH

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

22 Oct 2020 11:21

Last Modified:

22 Oct 2020 11:28

Publisher DOI:

10.1002/anie.201503312

PubMed ID:

26015026

Uncontrolled Keywords:

breath analysis high-resolution mass spectrometry ketamine pharmacokinetics secondary electrospray ionization

BORIS DOI:

10.7892/boris.147236

URI:

https://boris.unibe.ch/id/eprint/147236

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