Quantitation of the EEG and pharmacodynamic modelling of hypnotic drugs: etomidate as an example

Six volunteers were subjected to an infusion of etomidate designed to generate linearly increasing plasma concentrations with a slope of 0.05 microgram ml-1 min-1. Cessation of infusion was determined by the occurrence of burst suppression patterns on the EEG. Infusion was restarted when the volunteers recovered personal and temporal orientation. This cycle was repeated twice. The drug input function, the pharmacokinetic parameters of etomidate as derived from a 'least squares' fit, and the median EEG frequency were used to establish a pharmacological model of etomidate. Two modelling procedures, the pharmacokinetic-pharmacodynamic, and the input-output modelling procedure, are compared. These procedures yield different results with respect to the kinetic data. As one possible explanation, a different pharmacokinetic behaviour of etomidate in the venous blood and at the site of drug action is discussed.