Precision Dosing Guide May Improve Outcomes for Infants Receiving Cardiac Surgery

Published June 2019 | Clinical Pharmacokinetics

Experts at Cincinnati Children’s have detailed the first age-appropriate dosing model for newborns and infants who need the drug milrinone to prevent low cardiac output syndrome after receiving cardiac surgery—including cases that involve acute kidney injury (AKI).

Milrinone is widely prescribed to prevent low cardiac output syndrome, with some studies of how the drug affects pediatric patients dating back to the 1990s. However, minimal pharmacokinetic data has been gathered to show how differently the drug behaves when infants also have AKI.

“This is the first study to identify dosing regimens across the age of 0–1 year based on AKI stages,” the co-authors state. “This developed pharmacokinetic model will facilitate informed precision dosing of milrinone in neonates and infants with or without AKI.”

The study involved analyzing serum levels of milrinone from 92 infants and tracking AKI injury stages. They found that milrinone clearance in patients with AKI was significantly lower than that in patients with no AKI.

The team determined that body weight and maturation function were significant predictors of drug clearance, which allowed them to set drug-infusion rates for three age groups of infants across the stages of AKI injury.

“The implications of developmental changes in pharmacokinetics have increasingly been acknowledged as important for age-appropriate precision dosing in young children,” the co-authors state. “The finding in this study adds additional insights on the developmental pharmacokinetics and pharmacotherapy in very young children such as neonates and infants following cardiac surgery.”

Cincinnati Children’s co-authors included first author Tomoyuki Mizuno, PhD, senior author Alexander Vinks, PharmD, PhD, Zhiqian Gao, PhD, Jeffrey Alten, MD, David Cooper, MD, MPH, and Stuart Goldstein, MD.

An image showing milrinone clearance rates according to acute kidney injury status.

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A photo of Alexander Vinks.

Alexander Vinks, PharmD, PhD


Mizuno T, Gist KM, Gao Z, Wempe MF, Alten J, Cooper DS, Goldstein SL, Vinks AA. Developmental Pharmacokinetics and Age-Appropriate Dosing Design of Milrinone in Neonates and Infants with Acute Kidney Injury Following Cardiac Surgery. Clin Pharmacokinet. 2019 Jun;58(6):793-803.