Background: In vitro studies have shown that ibuprofen (IBU) may interfere with bilirubin-albumin binding at concentrations of 100 microg/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 microg/mL and exceptionally above 100 microg/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 microg/mL. Only a concentration of 200 microg/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 microg/mL, however it retrieves no significant displacement over a range of concentrations up to and including 100 microg/mL, i.e. within the range of in vivo concentrations at the recommended dose regimen.
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