Classification of drugs on the basis of bilirubin-displacing effect on human serum albumin.

Abstract

The classification of drugs on the basis of binding sites on human serum albumin was studied by means of displacement experiments with bilirubin. The displacement of bilirubin by various drugs was evaluated through the kinetic measurement of free bilirubin concentration based on oxidation with hydrogen peroxide and peroxidase. The drugs tested could be classified into three groups, I, II and III. Oxyphenbutazone, phenylbutazone, sulfinpyrazone, ketophenylbutazone, glibenclamide, tolbutamide, sulfisoxazole, warfarin, salicylic acid and furosemide (group I drugs) effciently displaced bilirubin. Flufenamic acid, mefenamic acid, ibuprofen, acetohexamide and ethacrynic acid (group II drugs) did not displace bilirubin at a low molar ratio (drug / albumin<1.5), but did displace it at a high molar ratio. Clofibrate, buformin and phenytoin (group III drugs) did not displace bilirubin. These results suggested that (1) the primary binding site and secondary binding site for the group I drugs were identical or very close to the bilirubin-binding site, (2) the primary binding site of the group II drugs was independent of the bilirubin-binding site, but a secondary site was close to it, (3) the binding site of the group III drugs was independent of the bilirubin site.