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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)749-758
Number of pages10
JournalAmerican journal of perinatology
Volume34
Issue number8
DOIs
StatePublished - Jul 1 2017

Keywords

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

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    Giaccone, A., Zuppa, A. F., Sood, B., Cohen, M. S., O'Byrne, M. L., Moorthy, G., Mathur, A., & Kirpalani, H. (2017). Milrinone Pharmacokinetics and Pharmacodynamics in Neonates with Persistent Pulmonary Hypertension of the Newborn. American journal of perinatology, 34(8), 749-758. https://doi.org/10.1055/s-0036-1597996