Acetaminophen pharmacokinetics in infants and children with congenital heart disease

• DOI: 10.1111/pan.14579
• Publication Date: 2022-10-20T14:18:13Z
• Authors: Jay Holladay; Peter Winch; James Morse; Brian J. Anderson; Christopher T. McKee; Julie Rice‐Weimer; Joseph D. Tobias
• Keywords: Acetaminophen

Acetaminophen is routinely used for perioperative analgesia in children undergoing major surgical procedures. There are few estimates of acetaminophen pharmacokinetic parameters with congenital heart disease, especially those cyanotic disease.The current study prospectively investigated differences pharmacokinetics following surgery using cardiopulmonary bypass and acyanotic disease.Children (2-6 years, 9-23 kg) presenting median sternotomy Fontan palliation (cyanotic patients) or two ventricle repair (acyanotic were eligible inclusion. A single intravenous dose (15 mg/kg) was administered at the start sternal closure after separation from bypass. The time-course concentrations described non-linear mixed effects models. One two-compartment disposition models first-order elimination tested. Pharmacokinetic parameter scaled allometry standardized to a 70 kg person.There 208 assayed 30 children, 15 cyanotic, disease. 2-compartment model best PK. Parameter (population variability, PPV%; 95% confidence interval, CI) clearance CL 15.3 L.h-1.70 kg-1 (22.2%; 13.8-16.7), intercompartment Q 45.4 (22.4%; 25.2-61.9), central volume distribution V1 33.5 L.70 (23.2%; 25.9-38.8), peripheral V2 32.1 (21.7%; 25.9-38.8). Neither nor differed between patients.Acetaminophen characterized cardiac children. Population similar other studies No detected patients