Publication: Paediatric Drugs
Abstract
Treatment options for pulmonary hypertension associated with bronchopulmonary dysplasia (BPD-PH) in premature neonates are limited, and improving nitric oxide bioavailability via oral L-citrulline is a potential therapeutic strategy that had not been pharmacokinetically characterized in this population. This study administered a single oral dose of L-citrulline to 10 premature neonates at risk of BPD-PH, using sparse sampling and non-compartmental analysis in Phoenix WinNonlin to characterize its pharmacokinetics and derive optimal dosing strategies via simulation. L-citrulline showed a short half-life of about 16 minutes, and simulations suggested doses of roughly 37.5-51.5 mg/kg given four times daily would achieve target steady-state concentrations. This first pharmacokinetic study of L-citrulline in neonates provides a foundation for future randomized trials evaluating enteral L-citrulline for BPD-PH.
Author(s): Fike CD, Avachat C, Birnbaum AK, Aschner JL, Sherwin CM
Published: 2022 年 10 月 31 日
Phoenix WinNonlin: Sparse-Sampling PK in Neonates
Phoenix WinNonlin's non-compartmental analysis handled sparse-sampling data from premature neonates in this L-citrulline study, informing a first-of-its-kind dosing strategy. As part of a Phoenix platform used by more than 1,600 companies across 60 countries, Phoenix WinNonlin can be paired with AI PK Reports to turn an analysis into a complete PK document in minutes rather than days.
