title: Drug Pharmacokinetics Determined by Real-Time Analysis of Mouse Breath.
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.
authors.affiliation: Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich (Switzerland).|Institute of Atmospheric Environmental Safety and Pollution Control, Jinan University, Huangpu Road West 601, Guangzhou 510632 (China).
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich (Switzerland).
authors.forename: Pablo
authors.initials: P
authors.lastname: Martinez-Lozano Sinues
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland).|University of Warwick, Warwick Medical School, Gibbet Hill Road, Coventry, CV4 AL7 (United Kingdom).
authors.forename: Robert
authors.initials: R
authors.lastname: Dallmann
authors.affiliation: Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich (Switzerland).
authors.forename: Lukas
authors.initials: L
authors.lastname: Bregy
authors.affiliation: Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich (Switzerland).
authors.forename: Maija
authors.initials: M
authors.lastname: Hollmén
authors.affiliation: Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich (Switzerland).
authors.forename: Steven
authors.initials: S
authors.lastname: Proulx
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland).
authors.forename: Steven A
authors.initials: SA
authors.lastname: Brown
authors.affiliation: Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich (Switzerland).
authors.forename: Michael
authors.initials: M
authors.lastname: Detmar
authors.affiliation: Pulmonary Division, University Hospital Zürich, Rämistrasse 100, 8091 Zürich (Switzerland).
authors.forename: Malcolm
authors.initials: M
authors.lastname: Kohler
authors.affiliation: Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich (Switzerland). Zenobi@org.chem.ethz.ch.
authors.forename: Renato
authors.initials: R
authors.lastname: Zenobi
mesh_terms: D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D001944:Breath Tests / Q000295:instrumentation / Q000379:methods*; D004867:Equipment Design; D007274:Injections, Intraperitoneal; D007649:Ketamine / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D051379:Mice; D015742:Propofol / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D021241:Spectrometry, Mass, Electrospray Ionization / Q000295:instrumentation / Q000379:methods*; D014635:Valproic Acid / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D000700:Analgesics; D018686:Anesthetics, Intravenous; D000927:Anticonvulsants; D014635:Valproic Acid; D007649:Ketamine; D015742:Propofol
keywords: breath analysis; high-resolution mass spectrometry; ketamine; pharmacokinetics; secondary electrospray ionization