Indomethacin and bilirubin-albumin binding

We studied the effects of indomethacin on the bilirubin binding of albumin using the hydroxybenzene azobenzoic acid (HBABA) dye binding method, the estimation of unbound bilirubin concentration (UBC) by the horseradish peroxidase assay and the whole blood fractionation (WBF) technique. The addition of up to 2 micrograms/ml of indomethacin, which is the level obtained with an 0.2 mg/kg dose, did not decrease the mean HBABA dye binding capacity of 29 icteric sera or increase the mean UBC of 11 icteric sera. There was also no additional displacement of bilirubin in 5 icteric sera measured by the WBF technique. However, the addition of 10-40 micrograms/ml of drug, which is the level that would be achieved if a 2 mg/kg dose of indomethacin were administered, resulted in a significant reduction of HBABA in 15 icteric sera (81.74-57.3%, p less than 0.005) and a significant increase of UBC in 11 icteric sera (6.17-37.2 nM/l, p less than 0.001). Therefore, no displacement of bilirubin from albumin occurred in the presence of usual therapeutic level of indomethacin; higher levels displaced bilirubin.