Pharmacokinetics of Etomidate, a New Intravenous Anesthetic

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Abstract

Etomidate sulfate, 0.3 mg/kg, was administered intravenously to eight patients and venous blood samples were drawn at intervals for the subsequent 10 hours. Plasma etomidate was determined by mass fragmentography. Plasma concentrations were fitted to a triexponential equation consistent with a three-compartment open pharmacokinetic model. Mean (±SD) variables were: initial t1/2, 2.6 ± 1.3 min; intermediate t1/2, 28.7 ± 14.0 min; apparent elimination t1/2, 4.6 ± 2.6 hours; volume of the central compartment, 23.2 ± 11.4 1; total apparent volume of distribution, 4.5 ± 2.2 1/kg; fraction of drug in the central compartment, 7 per cent; total plasma clearance, 860 ± 230 ml/min. Total blood clearance was estimated to be 754 ml/min and hepatic clearance, 739 ml/min. The large apparent volume of distribution indicates considerable tissue uptake. The hepatic clearance, being about 50 per cent of hepatic blood flow, indicates that changes in hepatic blood flow or hepatic metabolism will have only moderate effects on etomidate disposition.

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