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

Text anie.201503312.pdf - Published Version Restricted to registered users only Available under License Publisher holds Copyright. Download (1MB)

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.

Interest & Impact

Downloads

1 since deposited on 22 Oct 2020
0 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item