Milrinone Pharmacokinetics and Pharmacodynamics in Neonates with Persistent Pulmonary Hypertension of the Newborn

Annie Giaccone; Athena F. Zuppa; Beena Sood; Meryl S. Cohen; Michael L. O'Byrne; Ganesh Moorthy; Amit Mathur; Haresh Kirpalani

doi:10.1055/s-0036-1597996

American Journal of Perinatology, Table of Contents

Am J Perinatol 2017; 34(08): 749-758
DOI: 10.1055/s-0036-1597996

Original Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Milrinone Pharmacokinetics and Pharmacodynamics in Neonates with Persistent Pulmonary Hypertension of the Newborn

Authors

Annie Giaccone

¹Department of Pediatrics, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania

²Section of Neonatology, Reading Hospital, West Reading, Pennsylvania
Athena F. Zuppa

³Department 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
Beena Sood

⁴Department of Pediatrics, Children's Hospital of Michigan and Wayne State University School of Medicine, Detroit, Michigan
Meryl S. Cohen

¹Department of Pediatrics, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
Michael L. O'Byrne

¹Department of Pediatrics, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania

⁵Department of Pediatrics, Children's National Health System and George Washington University School of Medicine and Health Sciences, Washington, District of Columbia
Ganesh Moorthy

³Department 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
Amit Mathur

⁶Department of Pediatrics, St. Louis Children's Hospital and Washington University School of Medicine, St. Louis, Missouri
Haresh Kirpalani

¹Department of Pediatrics, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania

Abstract

Objective To 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.

Design Randomized, open label pilot study.

Setting Multicenter; level 3 and level 4 neonatal intensive care units.

Patients Six infants ≥34 weeks' gestational age and <10 days of life with persistent hypoxemia receiving inhaled nitric oxide.

Intervention Intravenous 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 Results The 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.

Conclusion The 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.

Keywords

persistent pulmonary hypertension of the newborn - meconium aspiration syndrome - milrinone - phosphodiesterase 3 inhibitors - vasodilator agents - pharmacokinetics

Full Text

References

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