Oral Ibuprofen Is More Effective than Intravenous Ibuprofen for Closure of a Patent Ductus Arteriosus: Can Pharmacokinetic Modeling Help Us to Understand Why?

Introduction: Oral ibuprofen is more effective than intravenous (IV) ibuprofen for closure of a patent ductus arteriosus (PDA). This study explored whether higher concentrations of the biologically active S-enantiomer or increased R- to S-conversion following oral dosing could explain this finding. Methods: Two datasets containing 370 S- and R-ibuprofen concentrations from 95 neonates with PDA treated with oral (n = 27, 28%) or IV ibuprofen were analyzed using nonlinear mixed effects modeling. Concentration-time profiles in typical neonates were explored and compared in different dosing or R- to S-conversion scenarios. Results: Postnatal age (PNA), gestational age (GA), and being small for GA impacted S- and R-ibuprofen clearance. Upon oral dosing, S-ibuprofen concentrations were lower compared to IV ibuprofen for a large part of the dosing interval. We could show that R- to S-conversion will not exceed 45%. Exploration of a 30% presystemic R- to S-conversion resulted in a 25–32% increase in S-ibuprofen exposure following oral administration with AUC72h values varying between 700–2,213 mg*h/L (oral) and 531–1,762 (IV) for the standard or 1,704–2,893 (oral) and 1,295–2,271 mg*h/L (IV) for PNA-based dosing. Discussion: The absence of higher S-ibuprofen concentrations does not support a beneficial concentration-time profile after oral dosing. While a fraction of up to 45% presystemic R- to S-conversion could not be ruled out, the impact of such a low conversion might be only relevant for the standard but not high dosing regimens, considering reported exposure-response targets. Perhaps, the lack of high peak concentrations observed following IV dosing may play a role in the observed effects upon oral dosing.

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch

Verweise und Beziehungen

• Erschienen in: Oral Ibuprofen Is More Effective than Intravenous Ibuprofen for Closure of a Patent Ductus Arteriosus: Can Pharmacokinetic Modeling Help Us to Understand Why? ; volume:120 ; number:1 ; year:2023 ; pages:81-89 ; extent:9 ; Neonatology ; 120, Heft 1 (2023), 81-89 (gesamt 9)

Beteiligte, Orts- und Zeitangaben

• Urheber: Smit, Cornelis ; Engbers, Aline G.J. ; Samiee-Zafarghandy, Samira ; van Donge, Tamara ; Simons, Sinno H.P. ; Flint, Robert B. ; Pfister, Marc ; Knibbe, Catherijne A.J. ; van den Anker, John N.

Weitere Informationen

• DOI: 10.1159/000526210
• URN: urn:nbn:de:101:1-2023031523315504465122
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 14.08.2025, 11:01 MESZ