Impaired plasma protein binding of phenytoin in uremia and displacement effect of salicylic acid

Abstract

The plasma protein binding of phenytoin (DPH) was studied by equilibrium dialysis at 37° C in plasma from uremic patients and healthy subjects. Scatchard plot analyses demonstrated a decreased association constant K_afor the DPH-albumin interaction in the uremic plasma (mean 1.76 . 10³ M⁻¹ ± SD 0.12 and a mean 4.10 10³ M⁻¹ ± SD 0.24 in normal plasma). Studies on separated fractions of serum did not indicate any significant binding of DPH to proteins other than albumin. The nonlinear mathematical relationship between bound DPH and serum albumin could be linearized at low drug concentrations by plotting the ratio of bound/unbound DPH against albumin concentration. The displacement effect of salicylic acid at a concentration of 276 μg/ml (2mM) on DPH was considerable in plasma from normal subjects. In uremic plasma the effect was of a much smaller magnitude.