title: 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 microg/mL and above.
  
  
  OBJECTIVE
  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.
authors.affiliation: SGS Cephac Europe, Saint-Benoît Cedex, France.
authors.forename: C
authors.initials: C
authors.lastname: Diot
authors.forename: Y
authors.initials: Y
authors.lastname: Kibleur
authors.forename: L
authors.initials: L
authors.lastname: Desfrere
mesh_terms: D000418:Albumins / Q000378:metabolism*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D001663:Bilirubin / Q000378:metabolism*; D001665:Binding Sites / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy*; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D066298:In Vitro Techniques; D007231:Infant, Newborn; D015997:Neonatal Screening / Q000592:standards; D009994:Osmolar Concentration; D011485:Protein Binding / Q000187:drug effects
chemical_list: D000418:Albumins; D018712:Analgesics, Non-Narcotic; D001663:Bilirubin; D007052:Ibuprofen