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Study of multiple binding constants of dexamethasone with human serum albumin by capillary electrophoresis-frontal analysis and multivariate regression

Zhao, Peng, Zhu, Guijie, Zhang, Weibing, Zhang, Lihua, Liang, Zhen, Zhang, Yukui
Analytical and bioanalytical chemistry 2009 v.393 no.1 pp. 257-261
binding sites, dexamethasone, equations, equilibrium theory, human serum albumin, multivariate analysis, pharmacokinetics
Studies into the interactions between drugs and human serum albumin (HSA) are extremely important for drug discovery, since HSA behaves as a carrier for external drugs and internal biological molecules. In this paper, to evaluate the pharmacokinetic and pharmacodynamic properties of dexamethasone (DXM), the interaction between DXM and HSA was studied by capillary electrophoresis-frontal analysis (CE-FA). According to the Klotz equation, four binding sites between DXM and HSA were obtained, and the average binding constant was 1.05 x 10³ M⁻¹. Furthermore, according to multiple equilibrium theory, based on the assumption that there are two types of binding site, the binding constant at one site was calculated to be 3.539 x 10³ M⁻¹, and the average of the other three was 1.234 x 10³ M⁻¹. In addition, to obtain the detailed binding information at each binding site, new equations were deduced by multivariate regression. The four binding constants of DXM and HSA were calculated to be 5.558 x 10¹ M⁻¹, 2.158 x 10⁴ M⁻¹, 7.312 x 10³ M⁻¹ and 2.043 x 10³ M⁻¹, respectively, which is helpful for detailed studies into the interactions between drugs and proteins with multiple binding sites. [graphic removed]