Population Pharmacokinetics and Pharmacodynamics of Brief Etomidate Infusion in Healthy Volunteers

Abstract

This study established the pharmacokinetic and pharmacodynamic relationships of the bispectral index (BIS) and Observer's Assessment of Alertness/Sedation (OAA/S) scale with effect site drug concentrations during and after brief etomidate infusion. Eighteen American Society of Anesthesiologists status I or II volunteers received etomidate (0.2%) infusion at 5 mg/min until the loss of eyelash reflexes, and spontaneous recovery was allowed. Data for plasma etomidate concentrations, BIS, and OAA/S were collected every minute and analyzed by NONMEM. A 2-compartment pharmacokinetic model and a pharmacodynamic sigmoid E(max) model fit the data best, with volumes of distribution at central and peripheral compartments of 4.45 and 74.90 L, respectively, and systemic and intercompartmental clearances of 0.63 and 3.16 L/min, respectively. t(1/2)k(e0) was 1.550 min. EC(50) values were 0.526 and 0.554 µg/mL, and gamma values were 2.25 and 6.24 for BIS and OAA/S, respectively. The prediction probability between OAA/S and BIS was 0.8. The slopes of the curves suggest that BIS is a better monitor of depth of sedation and hypnosis, whereas OAA/S may be more useful for monitoring sleep versus wakefulness. These results should be interpreted within the context of short-term etomidate infusion of less than 10 minutes.

Population pharmacokinetics of intravenous bolus etomidate in children over 6 months of age

“…In very recent, Kaneda et al. (9) conducted a population pharmacokinetic and pharmacodynamic study in adults, and derived a Vd of 79.4 l, which is very consistent with the present results. The reason for discrepancy in Vd estimation between the studies is unclear.…”

A Compar a Tive Study of Haemodynamic Effects of Propofol and Etomidate as an Induction Agent in Coronory Artery Surgery

“…Speed of infusion of both drugs were based on described pharmacokinetics and pharmacodynamics and reports found in the literature (0.50 and 0.75 mg/kg min for propofol and 0.1 mg/kg min for etomidate). 18,19,20,21 We have used morphine 0.1mg/kg as a premedication agent in all the cases. Concurrently, fentanyl 0.02 µg/kg was also administered before induction.…”

Clinical and Molecular Pharmacology of Etomidate

“…36 During brief etomidate infusions, bispectral index values correlate well with sedation scores. 37 Etomidate increases latency and decreases amplitude of auditory evoked potentials. 38 The duration of epileptiform activity following electroconvulsive therapy is longer after anesthetic induction with etomidate versus methohexital or propofol.…”

“…42 Etomidate is characterized by a large central volume of distribution, 4.5 litres/kg, and a very large peripheral volume of distribution, 74.9 litres/kg, due to its high solubility in fat. 30,37,43 The single bolus pharmacokinetic profile of plasma etomidate concentration is described by a three compartment model (Figure 3). 30 The fast, intermediate, and slow declines in plasma etomidate are thought to correspond to, respectively, distribution into highly perfused tissues, redistribution into peripheral tissues (mostly muscle), and terminal metabolism.…”