Abstract:

Objective To explore the characteristics of pharmacokinetics and influence factors after short-term injection of etomidate and to establish the population pharmacokinetics model. Methods Eleven pediatric patients with ASA Ⅰ-Ⅱ who scheduled to undergo elective surgeries under general anesthesia were selected. Etomidate of 60 μg·kg-1·min-1 was intravenously injected until the bispect ral index (BIS) value was below 50. The arterial blood samples were drawn at scheduled time points and the plasma concentration of etomidate was detected. Nonlinear mixed-effect model was adopted to establish the population pharmacokinetics model of etomidate. The effects of covariates (such as the age, height, and body mass, etc.) on pharmacokinetic parameters were analyzed. Results Initial analysis showed that the objective function values were 61, -63, and -77 for the one-compartment model, two-compartment model, and three-compartment model, respectively. The three-compartment model was most suitable for describing the pharmacokinetics of etomidate for children. The number of target functions further decreased after the body mass based allometric model was fitted. No other covariates that could significantly affect the pharmacokinetics were found. The typical values of population pharmacokinetic parameters were: V1=6.53×(WT/70)(L), V2=12.4×(WT/70)(L), V3=27.3×(WT/70)(L), Cl1=1.23×(WT/70)0.75(L/min), Cl2=1.42×(WT/70)0.75 (L/min), and Cl3=0.35×(WT/70)0.75. Conclusion Age does not affect the pharmacokinetics of etomidate, which suggests the metabolic pathway is mature at birth. The allometric effect of body weight on the pharmacokinetics of etomidate shows that for children with smaller body masses, their injection dose and rate of unit body mass should be higher.

Key words: etomidate, pediatric, population pharmacokinetics, allometrics