Unbound Bilirubin does not Increase during Ibuprofen Treatment of Patent Ductus Arteriosus in Preterm Infants

Objective To determine whether ibuprofen displaces bilirubin from albumin in preterm infants. Study design A total of 34 preterm neonates (<32 weeks gestation) treated by ibuprofen (10-5-5 mg/kg) were included in this prospective open-label study. Total bilirubin (TB), unbound bilirubin (UB), and ibuprofen concentrations were measured before, 1 hour, and 6 hours after the first dose; before and 1 hour after the second dose; and 72 hours after the beginning of treatment. The infants were screened by auditory brainstem responses and by neurologic examination at term. Results At baseline, TB, UB, apparent binding affinity of albumin (Ka), and albumin concentrations were 6.0 +/- 1.6 mg/dL, 1.9 +/- 2.2 mu g/dL, 14.1 +/- 5.8 L.mu mol(-1), and 28.7 +/- 2.3 g/L, respectively. Ibuprofen treatment had no effect on TB, UB, or Ka values. No correlation between UB or Ka and ibuprofen concentrations was found. No neurologic symptoms or significant modifications of auditory brainstem responses were observed at term. Conclusion Ibuprofen (10-5-5 mg/kg) did not displace bilirubin in preterm infants with a baseline TB concentration <8.8 mg/dL. (J Pediatr 2012;160:258-64).