Plasma protein binding and interaction studies with diflunisal, a new salicylate analgesic

Abstract

The binding of diflunisal to human serum albumin and normal human plasma has been studied by equilibrium dialysis at 37°, pH 4. The plasma protein binding data were analysed according to a Scatchard model with two independent classes of binding sites. The number of binding sites and the corresponding association constants have been estimated by nonlinear least-squares regression analysis: N 1 = 2.1, k 1 = 5.28 × 10 5M −1, N 2 = 7.7 and K 2 = 0.17 × 10 5M −1. At a difluni concentration of 50 μg/ml on average 99.83 per cent of the drug was bound to plasma proteins. The in vitro plasma protein binding of diflunisal was impaired by salicylic acid and phenprocoumon, while diflunisal itself was displaced from its primary binding sites in plasma by salicylic acid and bilirubin. Tolbutamide had no effect on the binding of diflunisal to plasma proteins.