In Vitro Spectroscopic Investigation of Losartan and Glipizide Competitive Binding to Glycated Albumin: A Comparative Study.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Losartan*/chemistry ; Losartan*/metabolism ; Glycated Serum Albumin* ; Serum Albumin*/chemistry ; Serum Albumin*/metabolism ; Protein Binding* ; Glipizide*/chemistry ; Glipizide*/metabolism ; Binding, Competitive*; Humans ; Binding Sites ; Glycation End Products, Advanced/metabolism ; Glycation End Products, Advanced/chemistry ; Circular Dichroism ; Serum Albumin, Human/chemistry ; Serum Albumin, Human/metabolism ; Spectrometry, Fluorescence ; Hypoglycemic Agents/chemistry ; Hypoglycemic Agents/metabolism

Understanding the interaction between pharmaceuticals and serum proteins is crucial for optimizing therapeutic strategies, especially in patients with coexisting chronic diseases. The primary goal of this study was to assess the potential changes in binding affinity and competition between glipizide (GLP, a second-generation sulfonylurea hypoglycemic drug) and losartan (LOS, a medication commonly prescribed for hypertension, particularly for patients with concurrent diabetes) with non-glycated (HSA) and glycated (gHSA GLC , gHSA FRC ) human serum albumin using multiple spectroscopic techniques (fluorescence, UV-visible absorption, and circular dichroism spectroscopy). The results indicated that FRC is a more effective glycation agent for HSA than GLC, significantly altering the albumin structure and affecting the microenvironment around critical amino acid residues, Trp-214 and Tyr. These modifications reduce the binding affinity of LOS and GLP to gHSA GLC and gHSA FRC , compared to HSA, resulting in less stable drug-protein complexes. The study revealed that LOS and GLP interact nonspecifically with the hydrophobic regions of the albumin surface in both binary (ligand-albumin) and ternary systems (ligand-albumin-ligand const ) and specifically saturate the binding sites within the protein molecule. Furthermore, the presence of an additional drug (GLP in the LOS-albumin complex or LOS in the GLP-albumin complex) complicates the interactions, likely leading to competitive binding or displacement of the initially bound drug in both non-glycated and glycated albumins. Analysis of the CD spectra suggests mutual interactions between GLP and LOS, underscoring the importance of closely monitoring patients co-administered these drugs, to ensure optimal therapeutic efficacy and safety.

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PCN-2-012/K/1/F Medical University of Silesia; PCN-2-013/K/2/F Medical University of Silesia

Keywords: AGEs; diabetes; drug–albumin binding; drug–drug interactions; glipizide; glycated albumin; losartan; polypharmacotherapy; spectroscopic investigation

JMS50MPO89 (Losartan)
0 (Glycated Serum Albumin)
0 (Serum Albumin)
X7WDT95N5C (Glipizide)
0 (Glycation End Products, Advanced)
ZIF514RVZR (Serum Albumin, Human)
0 (Hypoglycemic Agents)

Date Created: 20240914 Date Completed: 20240914 Latest Revision: 20240916

20250114

PMC11395140

10.3390/ijms25179698

39273644