Interaction of palmitic acid with losartan potassium at the binding sites of bovine serum albumin

Abstract

The binding of losartan potassium, an angiotensin II receptor antagonist, to bovine serum albumin was studied by equilibrium dialysis method (ED) in presence or absence of palmitic acid. The study was carried out using ranitidine and diazepam as site-1 and site-2 specific probe, respectively. Different analysis of binding of losartan to bovine serum albumin suggested two sets of association constants: high affinity association constant (k1 = 11.2 x 105 M-1) with low capacity (n1 = 2) and low affinity association (k2 = 2. 63 x 105 M-1) constant with high capacity (n2 = 10) at pH 7.4 and 27°C. During concurrent administration of palmitic acid and losartan potassium in presence or absence of ranitidine or diazepam, it was that found that palmitic acid causes the release of losartan potassium from its binding site on BSA resulting reduced binding of losartan potassium to BSA. The increment in free fraction of losartan potassium was from 13.1% to 47.2 % upon the addition of increased concentration of only palmitic acid at a concentration of 0 x 10-5 M to 16 x 10-5 M. In presence of ranitidine or diazepam as site specific probes, palmitic acid further increases the free fraction of losartan potassium were from 22.8% to 53.4% and 35.3 to 65.5%, respectively. This data provided the evidence of interaction of higher concentration of palmitic acid at the binding sites on BSA changing the pharmacokinetics properties of losartan potassium.