Kinetic and thermodynamic analysis of ligand interactions with albumin

Abstract

Drug interactions with serum albumin are of great use for the understanding of pharmacokinetic and pharmacodynamic mechanisms. In the paper interactions of atenolol, ibuprofen, phenylbutazone and warfarin with bovine serum albumin (BSA) were investigated in vitro by fluorescence quenching method. It was proved that the fluorescence quenching of BSA by ibuprofen, phenylbutazone and warfarin was mainly the result of static quenching due to complex formation, while in the case of atenolol BSA fluorescence was quenched dynamically. Binding constant К volumes at 25 °С were 3.3x102,3.6x106,1.4x105, and 7.9x10s M_1 for atenolol, ibuprofen, phenylbutazone and warfarin, respectively. Quenching analysis at different temperatures allowed calculating thermodynamic parameters such as AC, AH and AS. The results analysis according for thermodynamic principles achieved that the binding of ibuprofen and warfarin with BSA is enthalpy driven, whereas phenylbutazone binding is entropy driven. Interaction of atenolol with BSA was accompanied by equivalent changes of enthalpy and entropy. The significance of thermodynamic and kinetic data forthe interpretation of binding mechanisms is discussed.