Renal function and therapeutic concentrations of phenytoin

The plasma protein binding of phenytoin was studied in 40 adult patients with varying degrees of renal function impairment. The patients had stable renal function and no other condition known to alter phenytoin binding. Binding was measured by equilibrium dialysis, and the apparent affinity constant was calculated using the binding data and the measured serum albumin concentration. The apparent affinity of the drug decreased with a decrease in renal function. The decrease was most apparent in patients with creatinine clearances below 25 ml/min. The importance of altered binding on the therapeutic range is discussed, and a method of calculating equivalent therapeutic phenytoin concentrations from serum albumin and renal function is described.