[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).
Levron
J C
JC
JANSSEN Research Foundation, Laboratoires JANSSEN, Aubervilliers.
Assoune
P
P
D000328:Adult; D000367:Age Factors; D000368:Aged; D005045:Etomidate / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism; D008657:Metabolic Clearance Rate; D008723:Methohexital / Q000493:pharmacokinetics; D008875:Middle Aged; D015742:Propofol / Q000493:pharmacokinetics; D013874:Thiopental / Q000493:pharmacokinetics; D014018:Tissue Distribution
D008723:Methohexital; D013874:Thiopental; D015742:Propofol; D005045:Etomidate
Pharmacocinétique de l'étomidate.