Displacement of albumin-bound antimicrobial agents by bilirubin

The ability of bilirubin to displace antimicrobial agents from their binding sites on albumin was studied in vitro by equilibrium dialysis. Sulfonamides, tetracyclines, penicillins and cephalosporins of different degrees of protein binding were tested. It was found that bilirubin reduced the protein binding of all four classes of antimicrobial agents, although by varying degrees. This effect was most pronounced with the compounds which had the highest degree of protein binding, such as cloxacillin, cephazolin, methacycline and sulfisoxazole, all of which are bound greater than 80% by albumin. On the other hand, the drugs with less than 25% binding, such as ampicillin, cephalexine and tetracycline were not ostensibly displaced by bilirubin. Scatchard plots of the binding of sulfamethoxazole to albumin in the presence of 400 mumol/1 of bilirubin, showed that bilirubin almost completely displaced the sulfonamide molecule from the high affinity site on the albumin molecule. Reduced protein binding of drugs in hyperbilirubinemic infants may have pharmacokinetic significance.