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 i ndependent of inspired sevoflurane concentration over a defined dose r ange. in contrast, studies using rabbits have found that plasma concen trations and urinary excretion of fluoride ion are dose-dependent up t o 3% inspired sevoflurane. We measured sevoflurane metabolite concentr ations in adult male Sprague-Dawley rats and related them to inspired sevoflurane concentrations. When plasma concentrations and urinary exc retion of metabolites were measured in vivo, they were dependent on in spired anesthetic concentration at concentrations less than 1.25%, but became less dose-dependent at higher anesthetic concentrations. Sevof lurane metabolism by precision-cut liver slices in vitro became dose-i ndependent at more than 10-30 mu M sevoflurane. No evidence of substra te inhibition was observed. These data provide evidence that sevoflura ne metabolite concentrations are almost independent of inspired anesth etic concentration over at least part of the clinically used concentra tion range.