Effect of ibuprofen on bilirubin-albumin binding affinity in premature infants

Aim: To evaluate the effect of ibuprofen on bilirubin-albumin binding affinity and unbound bilirubin in premature infants. Study design: A prospective study with subjects serving as their own controls was performed on <30 weeks' gestational age infants with unconjugated hyperbilirubinemia and who received ibuprofen for patent ductus arteriosus. Infants with congenital malformation, TORCH infections, and conjugated hyperbilirubinemia were excluded. Total serum bilirubin (TSB) and unbound bilirubin (modified peroxidase test) were measured prior to (baseline) and after (follow-up) initiation of ibuprofen. The bilirubin/albumin equilibrium association binding constant was calculated using albumin, TSB, and unbound bilirubin. Results: Ten infants were studied. The mean TSB between baseline (5.9 +/- 1.7 mg/dL) was higher than that at follow-up [4.9 +/- 1.7 mg/dL]. Mean unbound bilirubin at baseline (0.75 +/- 0.65 mu g/dL) was similar to that at follow-up (0.63 +/- 0.46 mu g/dL). No difference existed between mean baseline binding constant (49 +/- 50 L/mu mol) and that at follow-up (44 +/- 36 L/mu mol). The ratio of unbound bilirubin with and without ibuprofen, index of displacing effect, was 0.88 (95% CI 0.63-1.14). Conclusions: Ibuprofen may not be associated with bilirubin displacing effect in relatively stable premature infants with mild to moderate unconjugated hyperbilirubinemia.