title: Population pharmacokinetics of pentobarbital in neonates, infants, and children after open heart surgery.
abstract: OBJECTIVE
  To determine the pharmacokinetics of pentobarbital in neonates, infants, and young children with congenital heart disease after open-heart surgery.
  
  
  METHODS
  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.affiliation: Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Athena F
authors.initials: AF
authors.lastname: Zuppa
authors.forename: Susan C
authors.initials: SC
authors.lastname: Nicolson
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Barrett
authors.forename: Marc R
authors.initials: MR
authors.lastname: Gastonguay
mesh_terms: D000367:Age Factors; D001835:Body Weight; D002675:Child, Preschool; D006330:Heart Defects, Congenital / Q000601:surgery*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000097:blood / Q000493:pharmacokinetics*; D007223:Infant; D007231:Infant, Newborn; D010424:Pentobarbital / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: D006993:Hypnotics and Sedatives; D010424:Pentobarbital