Tamara van Donge

Personalized use of ibuprofen in preterm neonates 99 6 What is already known on this topic • Oral ibuprofen appears to be the drug of choice for pharmacological closure of patent ductus arteriosus in preterm infants. • The current success rate of oral ibuprofen for closure of patent ductus arteriosus in the most preterm neonates is relatively low. • Lack of data on exposure-response relationship of oral ibuprofen, in preterm neonates with patent ductus arteriosus, may contribute to the limited success rate of this drug. What this study adds • In preterm neonates with patent ductus arteriosus plasma concentrations of ibuprofen, obtained 8 hours or more after administration of the first dose are predictive of the AUC 0-72h . • Preterm neonates with patent ductus arteriosus with an increased risk of a sub-therapeutic AUC 0-72h and, as a consequence, a potentially ineffective treatment can be identified in a very early stage. • Using a novel sampling strategy, clinical trials to investigate an individualized pharmacological approach for the closure of patent ductus arteriosus in preterm infants are feasible. Introduction Persistent patent ductus arteriosus (PDA) is a common condition in preterm neonates. Although the utility of pharmacological closure of a persistent PDA has been debated, an active targeted management of a hemodynamically significant PDA is currently viewed as an acceptable approach. 1-3 A network meta-analysis on the different pharmacotherapeutic options to close a PDA ranked high dose oral ibuprofen as the best therapeutic approach. 4 A recent Cochrane systematic review also favored oral ibuprofen over intravenous ibuprofen for failure to close a PDA and over indomethacin for risk of adverse events. 5 Nevertheless, the current success rate of oral ibuprofen for closure of PDA, in the most preterm neonates, remains