Protein binding of diazepam and digitoxin in uremic and normal serum

Abstract

The protein binding of diazepam and digitoxin in serum from uremie patients has been studied by equilibrium dialysis and compared to that in normal serum. Comparisons have also been made with isolated human serum albumin (HSA) from uremie and normal individuals. Diazepam and digitoxin are bound to different sites on HSA. Their binding was impaired in the serum from the patients when compared to that in the normal serum owing to decreased affinity constants for the binding to the primary sites on albumin. In the uremic serum the number of binding sites for diazepam is increased compared with the number in normal serum and HSA. For digitoxin the number of binding sites is larger both in the normal and the patient serum than that obtained with HSA. The fact that apparently an increased number of binding sites is made use of, is probably due to the presence of substances which inhibit the binding to the primary sites. The binding of the drugs was improved after charcoal-treatment of the uremie albumin at pH 3.0.