Population Pharmacokinetics of Pentobarbital in Neonates, Infants, and Children after Open Heart Surgery

• Published in: The Journal of pediatrics Vol. 159; no. 3; pp. 414 - 419.e3
• Main Authors: Zuppa, Athena F., Nicolson, Susan C., Barrett, Jeffrey S., Gastonguay, Marc R.
• Format: Journal Article
• Language: English
• Published: Maryland Heights, MO Mosby, Inc 01.09.2011; Elsevier
• Subjects: accounting; age; Age Factors; Biological and medical sciences; blood; Body Weight; Child, Preschool; children; General aspects; heart; Heart Defects, Congenital; Heart Defects, Congenital - surgery; heart diseases; Humans; Hypnotics and Sedatives; Hypnotics and Sedatives - blood; Hypnotics and Sedatives - pharmacokinetics; Infant; Infant, Newborn; Medical sciences; neonates; Pediatrics; pentobarbital; Pentobarbital - blood; Pentobarbital - pharmacokinetics; pharmacokinetics; surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Time Factors; Q; CL; t 1/2; PK; V1; FOCE-I; V2; Vd; Intercompartmental clearance; Clearance; Volume of distribution; Pharmacokinetic; Volume of peripheral compartment; Volume of central compartment; Elimination half-life; First-order conditional estimation with interaction; Human; Postoperative; Pediatrics; Psychotropic; Hypnotic; Infant; Cardiac surgery; Newborn; General anesthetic; Pentobarbital; Population; Sedative; Barbiturates; Pharmacokinetics; Child
• ISSN: 0022-3476; 1097-6833; 1097-6833
• DOI: 10.1016/j.jpeds.2011.04.021

To determine the pharmacokinetics of pentobarbital in neonates, infants, and young children with congenital heart disease after open-heart surgery. 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. 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. 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.