Ultrafiltration compared with equilibrium dialysis in the determination of unbound phenytoin in plasma

Protein binding of phenytoin (PHT) was studied in 36 patients with normal kidney function and six uremic patients. We compared a newly introduced ultrafiltration (UF) technique (EMIT Free Level System I) for measuring unbound PHT in plasma with an equilibrium dialysis (ED) method. The precision of the UF method was satisfactory (the CV within samples was 4.2%, and between days, 3.4%). PHT concentrations were measured with both homogeneous enzyme immunoassay and high performance liquid chromatography using plasma samples from epileptic patients. The values obtained agreed well. Unbound concentrations of PHT determined by the UF technique and ED were identical in both normal and uremic plasma obtained from patients under treatment. Unbound concentrations of PHT correlated significantly to total concentrations in both groups of patients. The investigated UF technique thus appears to be accurate for measuring unbound concentrations of PHT in plasma. Controlled clinical studies are required to show that this is a cost-effective clinical service.