A1 Refereed original research article in a scientific journal
Drug Pharmacokinetics Determined by Real-Time Analysis of Mouse Breath
Authors: Li X, Sinues PML, Dallmann R, Bregy L, Hollmen M, Proulx S, Brown SA, Detmar M, Kohler M, Zenobi R
Publisher: WILEY-V C H VERLAG GMBH
Publication year: 2015
Journal: Angewandte Chemie International Edition
Journal name in source: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Journal acronym: ANGEW CHEM INT EDIT
Volume: 54
Issue: 27
First page : 7815
Last page: 7818
Number of pages: 4
ISSN: 1433-7851
DOI: https://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 (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.
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.
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