The mechanism of interaction of hypoglycemic drugs, glimepiride and glipizide with human serum albumin (HSA) has been studied using fluorescence spectroscopy. The results are discussed in terms of the binding parameters, thermodynamics of the binding process, nature of forces involved in the interaction, identification of drug binding site on serum albumin and the fluorescence quenching mechanism involved. The association constants were of the order of 105 and glipizide was found to have much higher affinity for HSA than glimepiride at all temperatures. Thermodynamic parameters for the binding suggested that hydrophobic interactions are primarily involved in the binding of these drugs to HSA. However, glimepiride and glipizide appear to cause temperature-dependent conformational changes in the albumin molecule and, therefore, the nature of interaction varied with temperature. Glimepiride and glipizide bind to both site I and site II on HSA, but the primary interaction occurs at site II. The binding region in site II is different for the two drugs. Stern-Volmer analysis of quenching data indicated that tryptophan residues of HSA are not fully accessible to the drugs and a predominantly dynamic quenching mechanism is involved in the binding. Results can provide useful insight into prediction of competitive displacement of these drugs by other co-administered drugs and excipients, resulting in serious fluctuations of the blood glucose levels in diabetic patients. <alternatives> [...] </alternatives>
Financed by the National Centre for Research and Development under grant No. SP/I/1/77065/10 by the strategic scientific research and experimental development program:
SYNAT - “Interdisciplinary System for Interactive Scientific and Scientific-Technical Information”.