Article Text

Download PDFPDF

O-030 New Ibuprofen Dosing Strategy For Optimal Patent Ductus Arteriosus Closure In Preterm Neonates
  1. SHP Simons1,
  2. E Spaans2,
  3. IKM Reiss1,
  4. K Allegaert3,
  5. CA Knibbe4
  1. 1Neonatology, Erasmus University Medical Center – Sophia Children’s Hospital, Rotterdam, Netherlands
  2. 2Department of Pediatric Surgery and Intensive Care, Erasmus University Medical Center – Sophia Children’s Hospital, Rotterdam, Netherlands
  3. 3Neonatology, University Hospitals Leuven, Leuven, Belgium
  4. 4Clinical Pharmacy, St Antonius Hospital and Leiden Amsterdam Center for Drug Research, Nieuwegein/Leiden, Netherlands


Background and aims Ibuprofen is the drug of first choice to close a patent ductus arteriosus (PDA) in preterm neonates. The most commonly used 10–5–5 mg/kg/3days bolus dosing schedule is only effective in about 60% to 80% of patients, dependent on post natal age. We provide a new dosing regimen for ibuprofen, based on current available pharmacokinetic/pharmacodynamic (PK/PD) evidence that would result in the highest PDA closure rate.

Methods Simulation of different ibuprofen treatment strategies using NONMEM to predict the best pharmacodynamic effect based on available PK/PD data. Based on current evidence we assumed that ibuprofen efficacy depends on the cumulative time of threshold plasma level above 15 mg/l and that the volume of distribution is independent of postnatal age.

Results We show that the predicted plasma concentrations fit best after a 15 mg/kg ibuprofen loading dose followed by a post-natal age dependent continuous ibuprofen dose (table1). With this dosing schedule predicted plasma levels of 90% of patients continuously remain above threshold.

Abstract O-030 Table 1

Suggested ibuprofen bolus and continuous doses

Conclusions Based on PK/PD evidence, we suggest that the 10–5–5 mg/kg ibuprofen dosing schedule that has been used for PDA closure around the world during last decades is insufficient and should be improved. Our new dosing strategy needs further validation in daily clinical practice, but we expect a very high PDA closure rate.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.