Population pharmacokinetics of pentobarbital in neonates, infants, and children after open heart surgery

J Pediatr. 2011 Sep;159(3):414-419.e1-3. doi: 10.1016/j.jpeds.2011.04.021. Epub 2011 Jun 12.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Body Weight
  • Child, Preschool
  • Heart Defects, Congenital / surgery*
  • Humans
  • Hypnotics and Sedatives / blood
  • Hypnotics and Sedatives / pharmacokinetics*
  • Infant
  • Infant, Newborn
  • Pentobarbital / blood
  • Pentobarbital / pharmacokinetics*
  • Time Factors

Substances

  • Hypnotics and Sedatives
  • Pentobarbital