Mechanism of interaction of hypoglycemic agents glimepiride and glipizide with human serum albumin

Abstract

Abstract: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 10 5 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.

Glibenclamide-pregnenolone derivative has greater hypoglycemic effects and biodistribution than glibenclamide-OH in alloxan-rats

“…These data suggest that the steroid nucleus it is important for the hypoglycemic effects of the glibenclamide-pregnenolone derivative and possibly this is conditioned by degree of lipophilicity induced by steroid nucleus. This premise is supported by other studies 24 which indicate that changes in the structural chemical of glibenclamide to form some glibenclamide derivatives such as glimepiride and glipizide show variations in degree of lipophilicity and changes in glucose concentration.…”

Analysis of multi-site drug–protein interactions by high-performance affinity chromatography: Binding by glimepiride to normal or glycated human serum albumin

“…This method allowed for the preparation of a stable 50 μM glimepiride solution, which could then be used in further dilution steps to prepare working solutions for the chromatographic studies. Although glimepiride is a weak acid (p K a , 6.3), the pH of the final buffered solutions was not affected by the presence of this drug at the concentrations of this agent that were employed in this study [49]. …”

“…Previous work based on fluorescence spectroscopy has used relatively non-polar solvents (e.g., 2.5–10% dimethyl sulfoxide) to make it possible to investigate the interactions of this drug with normal HSA [49–51]. This current report will use HPAC to examine these interactions directly in aqueous solutions and at a physiological pH, while also expanding such studies to see how glycation affects these binding processes.…”

Complexation of fluoroquinolone antibiotics with human serum albumin: A fluorescence quenching study

“…As collisional quenching involves diffusion through the medium and diffusion coefficients increase with increase in temperature; increase in K q values with increase in temperature shows that collisional quenching mechanism is predominantly involved [10]. On the other hand, decrease in quenching constants with increase in temperature shows the involvement of static quenching mechanism [36]. Based on the temperature-dependence of quenching constants data in Table 6 show that collisional quenching mechanism are predominantly involved in the case of ciprofloxacin hydrochloride and enrofloxacin.…”