Intravenous pharmacokinetic profile in rats of etomidate, a short-acting hypnotic drug

Abstract

Etomidate is a novel short-acting drug, whose pharmacokinetic profile was studied in 14 organs and tissues after i.v. administration to rats. Four dose levels, ranging from 224 to 1800 mug, were assayed between 1.75 and 112 min after administration. A three-compartment open linear model has been fitted to the plasma concentrations, assuming a central, peripheral and deep compartment. The fast component of the plasma curve, has a half-life of 1.19 min. Brain tissue rapidly enters in equilibrium with plasma and shows the highest concentration. Muscle, subcutaneous fat and possibly skin and connective tissues contribute most to the total amount of drug in the body. Many tissues are heterogeneous and exhibit combinations of central, peripheral and deep compartments. Elimination of etomidate occurs by ester-hydrolysis in plasma and in the liver with approximately equal rate constants. Metabolization of etomidate in the liver is a capacity-limited Michaelis-Menten process.