title: Post-operative elimination of sevoflurane anesthetic and hexafluoroisopropanol metabolite in exhaled breath: pharmacokinetic models for assessing liver function.
abstract: Sevoflurane (SEV), a commonly used anesthetic agent for invasive surgery, is directly eliminated via exhaled breath and indirectly by metabolic conversion to inorganic fluoride and hexafluoroisopropanol (HFIP), which is also eliminated in the breath. We studied the post-operative elimination of SEV and HFIP of six patients that had undergone a variety of surgeries lasting between 2.5 to 8.5 h using exhaled breath analysis. A classical three compartments pharmacokinetic model developed for the study of environmental contaminants was fitted to the breath data. We found that SEV kinetic behavior following surgery (for up to six days) is consistent across all subjects whereas the production and elimination of HFIP varies to some extent. We developed subject specific parameters for HFIP metabolism and interpreted the differences in the context of timing and dose of anesthesia, type of surgery, and specific host factors. We propose methods for assessing individual patient liver function using SEV as a probe molecule for assessing efficiency of liver metabolism to HFIP. This work is valuable not only for the clinical study of metabolism recovery, but potentially also for the study of the interaction of other manufactured and environmental compounds with human systems biology in controlled exposure and observational studies.
authors.affiliation: Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via del Risorgimento, 35 56126 Pisa, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Ghimenti
authors.forename: F
authors.initials: F
authors.lastname: Di Francesco
authors.forename: M
authors.initials: M
authors.lastname: Onor
authors.forename: M A
authors.initials: MA
authors.lastname: Stiegel
authors.forename: M G
authors.initials: MG
authors.lastname: Trivella
authors.forename: C
authors.initials: C
authors.lastname: Comite
authors.forename: N
authors.initials: N
authors.lastname: Catania
authors.forename: R
authors.initials: R
authors.lastname: Fuoco
authors.forename: J D
authors.initials: JD
authors.lastname: Pleil
mesh_terms: D000368:Aged; D000769:Anesthesia, Inhalation / Q000379:methods*; D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics; D001944:Breath Tests; D045853:Exhalation; D005260:Female; D005459:Fluorides / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008738:Methyl Ethers / Q000493:pharmacokinetics*; D008962:Models, Theoretical; D011184:Postoperative Period; D020005:Propanols / Q000493:pharmacokinetics*; D000077149:Sevoflurane; D006845:Hydrocarbons, Fluorinated
chemical_list: D018685:Anesthetics, Inhalation; D005459:Fluorides; D008738:Methyl Ethers; D020005:Propanols; D000077149:Sevoflurane; C001337:hexafluoroisopropanol; D006845:Hydrocarbons, Fluorinated