Binding of desloratadine and atenolol with bovine serum albumin and their in-vitro interactions

Abstract

Aims: The binding of atenolol a selective β1 receptor antagonist and desloratadine, an H1 receptor antagonist, to bovine serum albumin. Methods: The analysis of binding was studied by equilibrium dialysis method (ED) using ranitidine and diazepam as site-1 and site-2 specific probe, respectively. Results: The study suggested two sets of association constants, for atenolol: high affinity association constant (k1 = 5 × 10-5 M-1) with low capacity (n1 = 2) and low affinity association constant (k2 = 2.5 × 10-5 M-1) with high capacity (n2 = 5), while for desloratadine: high affinity association constant (k1 = 45 × 10-5 M-1) with low capacity (n1 = 1.3) and low affinity association constant (k 2 = 5 × 10-5 M-1) with high capacity (n2 = 2.5) at pH 7.4 and 27 °C. During concurrent administration of atenolol and desloratadine in presence or absence of ranitidine or diazepam, desloratadine causes the release of atenolol from its binding site on BSA resulting reduced binding of atenolol to BSA. The increment in free fraction of atenolol was from 84.01% to 99 % upon the addition of increased concentration of only desloratadine at a concentration of 0 × 10-5 M to 14 × 10 -5 M. In presence of diazepam as site-II specific probes, desloratadine further increases the free fraction of atenolol was from 0.45% to 14.3%. Conclusion: These data were indicative for the interaction of higher concentration of desloratadine at the binding sites on BSA changing the pharmacokinetics properties of atenolol.