Drug interactions. III. Binding to and displacement from bovine serum albumin of barbiturates.

Publisher Website
Google Scholar
Abstract
Binding to and displacement from bovine serum albumin of 5 barbiturates, barbital, phenobarbital, pentobarbital, secobarbital and thiopental, were investigated by the dynamic dialysis method. Analysis of Scatchard plots indicated that there are marked differences in binding affinity and a parallelism in the relationship between chemical structure and their affinity. When these drugs are arranged in the order of their affinity for albumin molecule, there is a close correlation with pharmacological properties. The more highly protein-binding compounds are short-acting compounds with a rapid onset of action. They tend to be more rapidly degraded metabolically and are more potent hypnotics. For the study of competitive inhibition on the binding between barbiturate and albumin, thiopental was used as the test drug and chlorpropamide and lauric acid as the competitors. Substantial inhibition of binding of thiopental to albumin was found in both competitors with molar concentration of 0.7-1.0 times that of thiopental, at a ratio of 7 mol thiopental/mol of albumin. The competitive effect of lauric acid to inhibit binding of thiopental to serum albumin appears to be greater than that of chlorpropamide.