[Pharmacokinetics of etomidate].

Etomidate is the ester of a carboxylated imidazole. This lipophilic (octanol/water partition coefficient: 1000) and weak base (pKa = 4.5) is a potent short-acting hypnotic agent, which can be used for anaesthetic induction or maintenance. The plasma concentration curve fits an open three compartment pharmacokinetic model, with distribution half-lives of 2.6 and 20 min, and terminal elimination half-life of about 4-5 h. Hypnotic plasma concentrations (greater than 0.2 microgram.ml-1) are observed during the intermediate distribution phase (t1/2 approximately 20 min); they reflect the short lasting pharmacodynamic effect. The slow elimination phase is of importance for intravenous infusions lasting more than 2 h; it is recommended to decrease by half the maintenance dose (0.005 mg.kg-1.min-1) so as to prevent a cumulative effect. Etomidate is hydrolysed by hepatic esterases to the corresponding carboxylic acid, which is inactive. The pharmacokinetics of etomidate are altered in the elderly, with a decrease initial distribution volume and clearance (a decreased of 2 ml.min-1.kg-1 every decade) as well as in cirrhotic patients (a 100% increase in terminal half-life).