Drug Pharmacokinetics Determined by Real‐Time Analysis of Mouse Breath |
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Authors: | Dr Xue Li Dr Pablo Martinez‐Lozano Sinues Dr Robert Dallmann Lukas Bregy Dr Maija Hollmén Dr Steven Proulx Prof Steven A Brown Prof Michael Detmar Prof Malcolm Kohler Prof Renato Zenobi |
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Institution: | 1. Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich (Switzerland);2. Institute of Atmospheric Environmental Safety and Pollution Control, Jinan University, Huangpu Road West 601, Guangzhou 510632 (China);3. Institute of Pharmacology and Toxicology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland);4. University of Warwick, Warwick Medical School, Gibbet Hill Road, Coventry, CV4 AL7 (United Kingdom);5. Pulmonary Division, University Hospital Zürich, R?mistrasse 100, 8091 Zürich (Switzerland) |
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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 (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. |
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Keywords: | breath analysis high‐resolution mass spectrometry ketamine pharmacokinetics secondary electrospray ionization |
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