Displacement of bilirubin from albumin by ibuprofen in vitro.

Ibuprofen binds to plasma albumin and could interfere with the binding of bilirubin in jaundiced newborn infants. Most clinical studies have not shown increased concentrations of unbound bilirubin (UB) in plasma from infants treated with ibuprofen for a patent ductus arteriosus. However, studies in vitro have not been equally conclusive. Plasma were obtained from routine samples from jaundiced newborn infants and pooled. Total and UB were measured with the peroxidase method after addition of ibuprofen or sulfisoxazole as a known bilirubin displacer. Final ibuprofen concentrations varied from 0.43 to 2.6 mM. Bilirubin concentrations were varied from 176 to 708 microM by adding bilirubin to plasma samples. Ibuprofen caused a linear increase in UB up to +54% at a concentration of 1.8 mM, compared with an increase of 87% by sulfisoxazole (1.32 mM). A double reciprocal plot of molar concentrations of bound versus UB at bilirubin concentrations ranging from 176 to 708 microM showed a competitive displacement of bilirubin by ibuprofen. The data indicate that ibuprofen is a competitive displacer of bilirubin in vitro. Ibuprofen should be used with caution in premature infants with a significant hyperbilirubinemia.