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 wasstudied by equilibrium dialysis method (ED) in presence or absence of palmitic acid. The study wascarried out using ranitidine and diazepam as site-1 and site-2 specific probe, respectively. Differentanalysis of binding of losartan to bovine serum albumin suggested two sets of association constantshigh affinity association constant (k1 = 11.2 x 105 M-1) with low capacity (n1 = 2) and low affinityassociation (k2 = 2. 63 x 105 M-1) constant with high capacity (n2 = 10) at pH 7.4 and 27°C. Duringconcurrent administration of palmitic acid and losartan potassium in presence or absence of ranitidineor diazepam, it was that found that palmitic acid causes the release of losartan potassium from itsbinding site on BSA resulting reduced binding of losartan potassium to BSA. The increment in freefraction of losartan potassium was from 13.1% to 47.2 % upon the addition of increased concentrationof only palmitic acid at a concentration of 0 x 10-5 M to 16 x 10-5 M. In presence of ranitidine ordiazepam as site specific probes, palmitic acid further increases the free fraction of losartan potassiumwere from 22.8% to 53.4% and 35.3 to 65.5%, respectively. This data provided the evidence ofinteraction of higher concentration of palmitic acid at the binding sites on BSA changing thepharmacokinetics properties of losartan potassium(AU)