Impaired Plasma Phenytoin Binding in Uremia

Abstract

Phenytoin binding to uremic plasma was studied in vitro. Inhibition of binding independent of albumin concentration was demonstrated. Acidification from pH 8 to pH 3 produced a small decrease in binding by normal plasma but no change or a small increase in binding by uremic plasma. After plasma was acidified to pH 3.0, passed through an anion-exchange resin and realkalinized to pH 8, the binding by uremic plasma was restored to near normal. The uremic abnormality causing impaired plasma drug binding is reversible and supports the concept that a competing ligand, tightly bound at physiologic pH, is responsible for impaired drug binding.