Isolation of peptides from uremic plasma that inhibit phenytoin binding to normal plasma proteins

The binding of many drugs to plasma proteins is altered in renal disease. Explanations include hypoproteinemia, alterations in the native structure of the binding protein, and competitive or noncompetitive inhibition. The binding of phenytoin to proteins was studied in plasma from patients with chronic renal failure by equilibrium dialysis at 37 degrees. Charcoal adsorption was used to normalize the binding. Substances that appeared to be peptides were isolated; they inhibited the binding of phenytoin to normal plasma proteins. The data suggest that the defect in phenytoin-protein binding in chronic renal failure may be due to competitive or noncompetitive inhibition by peptides.