A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Drug Pharmacokinetics Determined by Real-Time Analysis of Mouse Breath
Tekijät: Li X, Sinues PML, Dallmann R, Bregy L, Hollmen M, Proulx S, Brown SA, Detmar M, Kohler M, Zenobi R
Kustantaja: WILEY-V C H VERLAG GMBH
Julkaisuvuosi: 2015
Journal: Angewandte Chemie International Edition
Tietokannassa oleva lehden nimi: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Lehden akronyymi: ANGEW CHEM INT EDIT
Vuosikerta: 54
Numero: 27
Aloitussivu: 7815
Lopetussivu: 7818
Sivujen määrä: 4
ISSN: 1433-7851
DOI: https://doi.org/10.1002/anie.201503312
Tiivistelmä
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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