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Post-operative elimination of sevoflurane anesthetic and hexafluoroisopropanol metabolite in exhaled breath: Pharmacokinetic models for assessing liver function
Citation:
Ghimenti, S., F. Di Francesco, M. Onor, M. Stiegel, M. Trivella, C. Comite, N. Catania, R. Fuoco, AND J. Pleil. Post-operative elimination of sevoflurane anesthetic and hexafluoroisopropanol metabolite in exhaled breath: Pharmacokinetic models for assessing liver function. Journal of Breath Research. Institute of Physics Publishing, Bristol, Uk, 7(3):1-10, (2013).
Impact/Purpose:
The National Exposure Research Laboratory′s (NERL′s) Human Exposure and Atmospheric Sciences Division (HEASD) conducts research in support of EPA′s mission to protect human health and the environment. HEASD′s research program supports Goal 1 (Clean Air) and Goal 4 (Healthy People) of EPA′s strategic plan. More specifically, our division conducts research to characterize the movement of pollutants from the source to contact with humans. Our multidisciplinary research program produces Methods, Measurements, and Models to identify relationships between and characterize processes that link source emissions, environmental concentrations, human exposures, and target-tissue dose. The impact of these tools is improved regulatory programs and policies for EPA.
Description:
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.
URLs/Downloads:
SEVOREVISION16APRIL2013 FINAL FINAL.PDF (PDF, NA pp, 509.477 KB, about PDF)Journal of Breath Research
