Temperature Dependence of Phenytoin-Protein Binding in Serum

Phenytoin-protein binding was determined as a function of temperature in uremic patients with normal albumin and in uremic patients with hypoalbuminemia. Free phenytoin levels were determined in ultrafiltrates (MPS-1; Amicon, Lexington, MA, U.S.A.) from serum equilibrated at either 20, 25, 30, 35, or 40 degrees C. Scatchard analyses showed significant differences in phenytoin-protein binding affinity as a function of temperature. Linear regression plots of free phenytoin versus temperature showed the slopes of the uremic and uremic with hypoalbuminemia patients (0.546 and 0.535, respectively) to be 3 times that of patients with normal renal function (0.174). Free phenytoin was analyzed in 150 patients with normal renal function in whom the total phenytoin was in the range of 38.0-80.8 mumol/L. The ultrafiltrate, prepared at 22 +/- 0.5 degrees C, resulted in free phenytoin levels in the range of 3.2-8.3 mumol/L. We have established this as the therapeutic range for the patient population seen at this medical center.