Influence of chronic renal failure and hemodialysis on diflunisal plasma protein binding

Abstract

Diflunisal protein binding was studied by equilibrium dialysis at 37 degrees in plasma from healthy, uremic, and geriatric subjects. Binding data were computer analyzed assuming 2 classes of independent binding sites (Scatchard model). K1, the primary association constant for the diflunisal-albumin interaction, was substantially lower in uremic plasma (2.39 +/- 0.29 x 10(5) M-1) than in normal plasma (6.86 +/- 0.59 x 10(5) M-1). No difference was found between the number of primary diflunisal binding sites (N1) in uremic and normal plasma. In geriatric plasma neither K1 nor N1 differed from the normal values, indicating that decreased diflunisal plasma protein binding in the elderly is a result of lower plasma albumin concentration. Binding studies with plasma from uremic patients during hemodialysis revealed that free diflunisal rose from 0.46 +/- 0.04% at the start to 0.61 +/- 0.06% at the end of dialysis. Plasma free fatty acid concentrations rose similarly. In vitro displacement studies showed that oleic acid is a competitive inhibitor for the binding of diflunisal to human serum albumin. This may explain the decrease in diflunisal plasma binding at the end of hemodialysis treatment.