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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.

Objectives: When developing a policy on how information about medication and its side effects (SE) should be provided in pediatrics, it is crucial to know individual needs. This paper investigates teenagers' and parental attitudes on information on SE, before and after education on the nocebo effect (NE). Methods: This multicenter survey study included 226 teenagers (12–18 years) and 525 parents of patients (0–18 years). Questions assessed demographics, clinical characteristics and attitudes towards the amount of SE information before and after the explanation of NE. Results: Before NE education, 679 (93 %) participants preferred to receive SE information: 337 (45 %) about all possible SE and 360 (48 %) desired specific information (i.e., severe, common, visible, or long-term SE). After NE explanation, significantly more participants (58 %) wished to receive information about all possible SE (p < .001). When explaining SE, teenagers preferred positive framing more than parents (64 % vs. 54 %, p = .043). Conclusions: Most teenagers and parents wish to receive extensive SE information, even after explaining the NE, but variances in individual needs exist. Practice implications: This study emphasizes the importance of tailor-made communication strategies for providing information on medications to parents and their children.