Interactions of Sulfonylureas with Plasma Proteins

The binding of sulfonylureas to plasma proteins was studied by a fluorescence method, using 9-(4′-carboxyanilino)-6-chloro-2-methoxyacridine (III) and 1-anilinonaphthalene-8-sulfonic acid (IV) as fluorescence probes. Chlorpropamide, acetohexamide, and tolbutamide competed with IV but not with III in binding to bovine serum albumin. In the cases of glipizide (I) and glyburide (glibenclamide) (II), however, competitive binding between these drugs and III was observed. In contrast to the decrease in intensity, fluorescence enhancement of IV by I and by II was found in human serum albumin and in both human and bovine serum albumins, respectively. The fluorescence of warfarin in bovine serum albumin solution was increased by the addition of I. This may indicate the formation of ternary complexes between these drugs and the probe-protein complex; as a result, these drugs may enhance the protein binding of the probe or drugs that compete with the probe for the same binding sites. In comparison with other sulfonylureas, I and II bind to different but closely located sites on the protein with greater affinities.