A1 Refereed original research article in a scientific journal

Drug Pharmacokinetics Determined by Real-Time Analysis of Mouse Breath




AuthorsLi X, Sinues PML, Dallmann R, Bregy L, Hollmen M, Proulx S, Brown SA, Detmar M, Kohler M, Zenobi R

PublisherWILEY-V C H VERLAG GMBH

Publication year2015

JournalAngewandte Chemie International Edition

Journal name in sourceANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Journal acronymANGEW CHEM INT EDIT

Volume54

Issue27

First page 7815

Last page7818

Number of pages4

ISSN1433-7851

DOIhttps://doi.org/10.1002/anie.201503312(external)


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.



Last updated on 2024-26-11 at 18:53