title: Milrinone Pharmacokinetics and Pharmacodynamics in Neonates with Persistent Pulmonary Hypertension of the Newborn.
abstract: ObjectiveTo describe the pharmacokinetics and pharmacodynamics of milrinone in infants with persistent pulmonary hypertension of the newborn (PPHN) and to explore the impact of age on milrinone disposition.DesignRandomized, open label pilot study.SettingMulticenter; level 3 and level 4 neonatal intensive care units.PatientsSix infants ≥34 weeks' gestational age and<10 days of life with persistent hypoxemia receiving inhaled nitric oxide.InterventionIntravenous milrinone lactate in one of two dosing regimens: (1) low dose, 20 mcg/kg bolus followed by 0.2 mcg/kg/minute, and (2) standard dose, 50 mcg/kg bolus followed by 0.5 mcg/kg/minute.Measurements and Main ResultsThe final structural model was a two-compartment disposition model with interindividual variability estimated on clearance (CL). The estimated value of CL is 7.65 mL/minute/3.4 kg (3.05 mL/minute/kg). The addition of age improved the precision of the CL estimate, and CL increased with chronological age in days. The oxygenation index was highly variable within each participant and improved with time. There were no observed safety concerns in either dosing group.ConclusionThe CL of milrinone in newborns with PPHN is reduced and increases with age. In this pilot study, we did not see significant pharmacodynamic or safety effects associated with drug exposure.
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.|Section of Neonatology, Reading Hospital, West Reading, Pennsylvania.
authors.forename: Annie
authors.initials: A
authors.lastname: Giaccone
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Athena F
authors.initials: AF
authors.lastname: Zuppa
authors.affiliation: Department of Pediatrics, Children's Hospital of Michigan and Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Beena
authors.initials: B
authors.lastname: Sood
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Meryl S
authors.initials: MS
authors.lastname: Cohen
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.|Department of Pediatrics, Children's National Health System and George Washington University School of Medicine and Health Sciences, Washington, District of Columbia.
authors.forename: Michael L
authors.initials: ML
authors.lastname: O'Byrne
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Moorthy
authors.affiliation: Department of Pediatrics, St. Louis Children's Hospital and Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Amit
authors.initials: A
authors.lastname: Mathur
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Haresh
authors.initials: H
authors.lastname: Kirpalani
mesh_terms: D061605:Administration, Intravenous; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D045462:Endothelium-Dependent Relaxing Factors / Q000008:administration & dosage; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal / Q000706:statistics & numerical data; D008297:Male; D008657:Metabolic Clearance Rate; D020105:Milrinone / Q000008:administration & dosage / Q000493:pharmacokinetics; D009569:Nitric Oxide / Q000008:administration & dosage*; D010101:Oxygen Consumption / Q000187:drug effects; D010547:Persistent Fetal Circulation Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D002316:Cardiotonic Agents; D045462:Endothelium-Dependent Relaxing Factors; D009569:Nitric Oxide; D020105:Milrinone