Anesthesia & Analgesia, Vol 81, 576-580, Copyright © 1995 by International Anesthesia Research Society
Relationship of inspired anesthetic concentration to plasma concentration and urinary excretion of sevoflurane metabolites in rats
TP Malan Jr, T Sameshima, H Mata and EJ Frink Jr
Department of Anesthesiology, University of Arizona Health Sciences Center, Tucson 85724, USA.
In patients, plasma concentrations of sevoflurane metabolites may be
independent of inspired sevoflurane concentration over a defined dose
range. In contrast, studies using rabbits have found that plasma
concentrations and urinary excretion of fluoride ion are dose-dependent up
to 3% inspired sevoflurane. We measured sevoflurane metabolite
concentrations in adult male Sprague-Dawley rats and related them to
inspired sevoflurane concentrations. When plasma concentrations and urinary
excretion of metabolites were measured in vivo, they were dependent on
inspired anesthetic concentration at concentrations less than 1.25%, but
became less dose-dependent at higher anesthetic concentrations. Sevoflurane
metabolism by precision-cut liver slices in vitro became dose-independent
at more than 10-30 microM sevoflurane. No evidence of substrate inhibition
was observed. These data provide evidence that sevoflurane metabolite
concentrations are almost independent of inspired anesthetic concentration
over at least part of the clinically used concentration range.