RELATIONSHIP OF INSPIRED ANESTHETIC CONCENTRATION TO PLASMA-CONCENTRATION AND URINARY-EXCRETION OF SEVOFLURANE METABOLITES IN RATS

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 mu M 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.