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

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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 H2O2 and peroxidase. The drugs tested could be classified into 3 groups, I, II and III. Oxyphenbutazone, phenylbutazone, sulfinpyrazone, ketophenylbutazone, glibenclamide, tolbutamide, sulfisoxazole, warfarin, salicylic acid and furosemide (group I drugs) efficiently displaced bilirubin. Flufenamic acid, mefenamic acid, ibuprofen, acetohexamide and ethacrynic acid (groug II drugs) did not displace bilirubin at a low molar ratio (durg/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 the primary binding site and secondary binding site for the group I drugs were identical or very close to the bilirubin-binding site; the primary binding site of the group II drugs was independent of the bilirubin-binding site, but a secondary site was close to it; and the binding site of the group III drugs was independent of the bilirubin site.