BACKGROUND: Information has been very limited on the population pharmacokinetics (PK) of etomidate in pediatric patients. The purpose of this study was to characterize the PK of etomidate in children. METHODS: Forty-nine children aged over 6 months undergoing elective surgery received etomidate 0.3 mg·kg(-1) bolus i.v. within 15 s for anesthesia induction. Arterial blood samples were collected for 2 h after injection. A population nonlinear mixed effects modeling approach was used to characterize etomidate PK. Estimates were standardized to a 70-kg adult using allometric size models. RESULTS: Children had a median age of 4 years (0.53-13.21 years) and weight 15.7 kg (7.5-52 kg). PK of etomidate was best estimated using a three-compartment model with weight on systemic (Cl(1)) and inter-compartmental clearances (Cl(2), Cl(3)), central (V(1)), and peripheral compartment volumes (V(2), V(3)). The most significant PK covariate was age, with increasing age having reduced size-adjusted Cl(1), V(1), and V(3) (all P < 0.01). The estimates of PK parameter (standardized to 70-kg adult) for a typical 4-year-old children were Cl(1) = 1.50 l·min(-1), Cl(2) = 1.95 l·min(-1), Cl(3) = 1.23 l·min(-1), V(1) = 9.51 l, V(2) = 11.0 l, and V(3) = 79.2 l, respectively. CONCLUSIONS: Owing to enhanced clearance and increased central compartment volume of etomidate, smaller (younger) children will require higher etomidate bolus dose than larger (older) children to achieve equivalent plasma concentrations. The dependence of Cl(1) and V(1) on age does not support weight-based etomidate dosing in smaller children.
BACKGROUND: Information has been very limited on the population pharmacokinetics (PK) of etomidate in pediatric patients. The purpose of this study was to characterize the PK of etomidate in children. METHODS: Forty-nine children aged over 6 months undergoing elective surgery received etomidate 0.3 mg·kg(-1) bolus i.v. within 15 s for anesthesia induction. Arterial blood samples were collected for 2 h after injection. A population nonlinear mixed effects modeling approach was used to characterize etomidate PK. Estimates were standardized to a 70-kg adult using allometric size models. RESULTS:Children had a median age of 4 years (0.53-13.21 years) and weight 15.7 kg (7.5-52 kg). PK of etomidate was best estimated using a three-compartment model with weight on systemic (Cl(1)) and inter-compartmental clearances (Cl(2), Cl(3)), central (V(1)), and peripheral compartment volumes (V(2), V(3)). The most significant PK covariate was age, with increasing age having reduced size-adjusted Cl(1), V(1), and V(3) (all P < 0.01). The estimates of PK parameter (standardized to 70-kg adult) for a typical 4-year-old children were Cl(1) = 1.50 l·min(-1), Cl(2) = 1.95 l·min(-1), Cl(3) = 1.23 l·min(-1), V(1) = 9.51 l, V(2) = 11.0 l, and V(3) = 79.2 l, respectively. CONCLUSIONS: Owing to enhanced clearance and increased central compartment volume of etomidate, smaller (younger) children will require higher etomidate bolus dose than larger (older) children to achieve equivalent plasma concentrations. The dependence of Cl(1) and V(1) on age does not support weight-based etomidate dosing in smaller children.
Authors: Felice Su; Mohammed H El-Komy; Gregory B Hammer; Adam Frymoyer; Carol A Cohane; David R Drover Journal: Biopharm Drug Dispos Date: 2015-01-21 Impact factor: 1.627