Effects of glycosylation of hypoglycaemic drug binding to serum albumin

✍ Scribed by Hikaru Koyama; Nobuyuki Sugioka; Akira Uno; Satoru Mori; Kenji Nakajima

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 143 KB
• Volume: 18
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/(sici)1099-081x(199712)18:9<791::aid-bdd66>3.0.co;2-1

✦ Synopsis

The binding properties of hypoglycaemic drugs to glycosylated human serum albumin (G-HSA) were investigated using a ¯uorescence quenching method. Displacement patterns between tolbutamide and Sudlow's-site-speci®c drugs to G-HSA were also investigated.

The order of the binding anities of these drugs to HSA was glibenclamide4 acetohexamide4tolbutamide5glicrazide4metfolmin. The order of the binding anities 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 aected saturable binding sites (I and II), whereas it did not in¯uence nonsaturable binding sites. The displacement patterns of tolbutamide binding between both albumins were not aected in the presence of site-I-or III-speci®c drugs, whereas the relative binding of tolbutamide to site-II-speci®c 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. &1997 John Wiley & Sons, Ltd.