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3019180 
Journal Article 
Drug Pharmacokinetics Determined by Real-Time Analysis of Mouse Breath 
Li, X; Martinez-Lozano Sinues, P; Dallmann, R; Bregy, L; Hollmén, M; Proulx, S; Brown, SA; Detmar, M; Kohler, M; Zenobi, R 
2015 
Yes 
Angewandte Chemie (International Edition)
ISSN: 1433-7851
EISSN: 1521-3773 
54 
27 
7815-7818 
English 
26015026 
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.