The <i>In vitro</i> Effects of Atenolol and Zinc Chloride on the Protein Binding of Amlodipine in Aqueous Medium

Abstract

An in vitro study of protein binding has been carried out to observe the influence of atenolol and zinc chloride on the protein binding of amlodipine by equilibrium dialysis method at 37±1 0C and at physiological pH (7.4). It has been found that zinc chloride lowered the affinity and percentage of protein binding of amlodipine to bovine serum albumin but atenolol has no such effect. The Scatchard plots were prepared to reveal the number of binding sites and the affinity for protein binding. It was seen that the highest percentage binding of amlodipine was 91% and the lowest was 74%. In the presence of atenolol, the highest and the lowest value of percentage of protein binding was 90% and 72%, respectively. In the presence of zinc chloride these values were 84% and 65% respectively. It is, thus, inferred that atenolol or its complex with amlodipine has no significant effect on percentage of protein binding of amlodipine. While zinc chloride or its complex with amlodipine can cause a decrease in percentage of protein binding of amlodipine. Complexation of amlodipine with zinc chloride might, therefore, displace the drug from the plasma and the displaced drugs may be redistributed, thus , increasing the free drug in plasma and tissue systems. This may change the pharmacokinetic properties of the drug and may affect the pharmacological and toxic effects. It is thus inferred that care and monitoring must be taken during combination therapy of amlodipine and zinc chloride.

Key words: Amlodipine, protein binding, binding site, equilibrium dialysis, Scatchard plot, atenolol, zinc chloride, combination therapy  

DOI = 10.3329/dujps.v7i1.1202

Dhaka Univ. J. Pharm. Sci. 7(1): 15-21, 2008 (June)