Gauging circadian variation in ketamine metabolism by real-time breath analysis.
The time-of-day of drug application is an important factor in maximizing efficacy and minimizing toxicity. Real-time in vivo mass spectrometric breath analysis of mice was deployed to investigate time-of-day variation in ketamine metabolism. Different production rates of ketamine metabolites, including the recently described anti-depressant hydroxynorketamine, were found in opposite circadian phases. Thus, breath analysis has potential as a rapid and 3Rs (Replacement, Reduction and Refinement) conforming screening method to estimate the time-dependence of drug metabolism.
Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
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http://orcid.org/0000-0001-5602-2880
P
Martinez-Lozano Sinues
Pulmonary Division, University Hospital Zurich, Zurich, Switzerland.
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M
Kohler
Institute of Pharmacology and Toxicology, University of Zurich, Switzerland.
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SA
Brown
Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
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R
Zenobi
Institute of Pharmacology and Toxicology, University of Zurich, Switzerland.
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http://orcid.org/0000-0002-7490-0218
R
Dallmann
D000818:Animals; D001944:Breath Tests; D057906:Circadian Clocks / Q000502:physiology; D007649:Ketamine / Q000032:analysis / Q000378:metabolism*; D013058:Mass Spectrometry; D051379:Mice
D007649:Ketamine