OBJECTIVES: To determine the pharmacokinetics of pentobarbital in neonates, infants, and young children with congenital heart disease after open-heart surgery. STUDY DESIGN: Thirty-five subjects (3.0 days-4.4 years) after open-heart surgery who received pentobarbital as standard of care were enrolled. Serial pharmacokinetic blood samples were obtained. A population-based, nonlinear mixed-effects modeling approach was used to characterize pentobarbital pharmacokinetics. RESULTS: A two-compartment model with weight as a co-variate allometrically expressed on clearance (CL), inter-compartmental clearance, central (V1) and peripheral volume of distributions, bypass grafting time as a co-variate on CL and V1, and age and ventricular physiology as co-variates on CL best described the pharmacokinetics. A typical infant (two-ventricle physiology, 6.9 kg, 5.2 months, and bypass grafting time of 60 minutes) had a CL of 0.12 L/hr/kg, V1 of 0.45 L/kg, and peripheral volume of distributions of 0.98 L/kg. The bypass grafting effect was poorly estimated. For subjects <12 months age, an age effect on CL remained after accounting for weight and was precisely estimated. CONCLUSIONS: Pentobarbital pharmacokinetics is influenced by age and weight. Subjects with single-ventricle physiology demonstrated a 15% decrease in clearance when compared with subjects with two-ventricle physiology.
OBJECTIVES: To determine the pharmacokinetics of pentobarbital in neonates, infants, and young children with congenital heart disease after open-heart surgery. STUDY DESIGN: Thirty-five subjects (3.0 days-4.4 years) after open-heart surgery who received pentobarbital as standard of care were enrolled. Serial pharmacokinetic blood samples were obtained. A population-based, nonlinear mixed-effects modeling approach was used to characterize pentobarbital pharmacokinetics. RESULTS: A two-compartment model with weight as a co-variate allometrically expressed on clearance (CL), inter-compartmental clearance, central (V1) and peripheral volume of distributions, bypass grafting time as a co-variate on CL and V1, and age and ventricular physiology as co-variates on CL best described the pharmacokinetics. A typical infant (two-ventricle physiology, 6.9 kg, 5.2 months, and bypass grafting time of 60 minutes) had a CL of 0.12 L/hr/kg, V1 of 0.45 L/kg, and peripheral volume of distributions of 0.98 L/kg. The bypass grafting effect was poorly estimated. For subjects <12 months age, an age effect on CL remained after accounting for weight and was precisely estimated. CONCLUSIONS:Pentobarbital pharmacokinetics is influenced by age and weight. Subjects with single-ventricle physiology demonstrated a 15% decrease in clearance when compared with subjects with two-ventricle physiology.
Authors: Veronica J Rooks; Taylor Chung; Linda Connor; David Zurakowski; Frederic A Hoffer; Keira P Mason; Patricia E Burrows Journal: AJR Am J Roentgenol Date: 2003-04 Impact factor: 3.959
Authors: Andrew J Kienstra; Mark A Ward; Fahimeh Sasan; Jill Hunter; M Craig Morriss; Charles G Macias Journal: Pediatr Emerg Care Date: 2004-08 Impact factor: 1.454
Authors: Susan M Abdel-Rahman; Gordon L Amidon; Ajay Kaul; Viera Lukacova; Alexander A Vinks; Gregory T Knipp Journal: Clin Ther Date: 2012-11 Impact factor: 3.393