Document resource
Objective The use of oral ibuprofen to treat haemodynamically significant patent ductus arteriosus (hsPDA) in premature neonates is common. However, among Chinese preterm neonates, the available pharmacokinetic (PK) findings for its enantiomers remain merely descriptive. This study aimed to characterise the PKs, dosing exposure and safety of oral ibuprofen in Chinese preterm infants treated with hsPDA.Design A pilot trial.Setting Three perinatal centres across Southwest China.Patients Preterm infants (≤35 weeks’ gestational age, ≥48 hours postnatal age) with suspected hsPDA (August 2022–May 2023).Intervention Oral ibuprofen (10, 5 and 5 mg/kg at 24-hour intervals) was used and sparse sampling was performed.Main outcome measures Plasma concentrations were analysed via ultrahigh-performance liquid chromatography–tandem mass spectrometry. The PK parameters were calculated via ADAPT 5 software. Adverse events and treatment efficacy were assessed.Results 14 neonates provided 42 plasma samples. The R-ibuprofen (R-IBU) concentrations were lower than the S-ibuprofen (S-IBU) concentrations. The clearance values for rac-ibuprofen (rac-IBU), R-IBU and S-IBU were 24.22±37.04, 206.1±143.1 and 12.67±26.53 mL/kg/hour, respectively. The area under the curve (AUC 0-72h) values for rac-IBU, R-IBU and S-IBU were 799.8±392.8, 75.9±51.9 and 537±246.4 µg hour/mL, respectively. DA closure was achieved in 8 (57%) infants. The indirect bilirubin level increased significantly following the administration of oral ibuprofen (p<0.05).Conclusions The recommended dosage regimen for Chinese preterm neonates with hsPDA may be insufficient to achieve targeted therapeutic exposure. Importantly, our study indicated that even at a relatively high dose, drug exposure might remain within the therapeutic window. Moreover, we observed a higher conversion ratio of R-IBU to S-IBU in these neonates than in adults. The use of ibuprofen may be associated with an elevated risk of jaundice in preterm infants.Trial registration number Chinese Clinical Trial Registry (ChiCTR2300067714).