Effects of glycosylation of hypoglycaemic drug binding to serum albumin.

The binding properties of hypoglycaemic drugs to glycosylated human serum albumin (G-HSA) were investigated using a fluorescence quenching method. Displacement patterns between tolbutamide and Sudlow's-site-specific drugs to G-HSA were also investigated. The order of the binding affinities of these drugs to HSA was glibenclamide > acetohexamide > tolbutamide > or = glicrazide > metfolmin. The order of the binding affinities were the same for G-HSA as for HSA. The ability of G-HSA to bind hypoglycaemic drugs, however, was much lower than that of HSA. Scatchard plots for the binding of tolbutamide to both albumins were biphasic. The glycosylation affected saturable binding sites (I and II), whereas it did not influence non-saturable binding sites. The displacement patterns of tolbutamide binding between both albumins were not affected in the presence of site-I- or III-specific drugs, whereas the relative binding of tolbutamide to site-II-specific drugs between the two albumins was remarkably changed. The glycosylation of HSA not only increases the unbound drug concentration but also changes the displacement pattern at site II. Our results suggest that the extensive glycosylation of plasma proteins in diabetic patients complicates drug-drug interactions beyond those seen in normal people.