Effect of ibuprofen on bilirubin–albumin binding in vitro at concentrations observed during treatment of patent ductus arteriosus

Abstract

Background In vitro studies have shown that ibuprofen (IBU) may interfere with bilirubin–albumin binding at concentrations of 100 µg/mL and above. Objectives The present study evaluates the in vitro bilirubin displacement over the range of IBU plasma concentrations observed in vivo during curative treatment of patent ductus arteriosus in preterm infants. Methods Considering that individual plasma concentrations obtained during the clinical development of IBU in preterm infants were ranging between 10 and 70 µg/mL and exceptionally above 100 µg/mL, we used the modified peroxidase method to determine total and unbound bilirubin concentrations without IBU and with IBU over this specific concentration range. Results Total bilirubin and albumin concentrations were respectively 6.6 mg/dL and 2.87 g/dL in pooled newborn plasma. No displacement of bilirubin from its albumin binding sites by IBU was observed over a range of concentrations from 10 to 100 µg/mL. Only a concentration of 200 µg/mL significantly increased the unbound bilirubin by 1.5-fold ( p = 0.0008). Conclusions This in vitro study confirms displacement of bilirubin by a high IBU concentration of 200 µg/mL, however it retrieves no significant displacement over a range of concentrations up to and including 100 µg/mL, i.e. within the range of in vivo concentrations at the recommended dose regimen.