Accuracy of three methods for predicting concentrations of free phenytoin

Predictions of free (unbound) serum phenytoin concentration by three methods were compared with results obtained by the Abbott TDx Free Phenytoin ultrafiltration and fluorescence-polarization immunoassay technique. Data were obtained for hospitalized adults who had been receiving phenytoin for at least five days and were free of renal or hepatic disease. Total phenytoin concentration was determined, and free phenytoin concentration was measured in ultrafiltrate at 25 degrees C. For each patient, measured concentrations of total phenytoin and albumin were used to predict free phenytoin concentrations by the Gugler method, the Sheiner-Tozer nomogram, and the Sheiner-Tozer equation. Mean measured percentages of free phenytoin were 17.79%, 12.13%, and 8.73%, respectively, for patients with albumin concentrations of less than 2 g/dL (n = 5), 2-3 g/dL (n = 18), and greater than 3 g/dL (n = 26). There was a strong correlation between actual and predicted free phenytoin concentrations for each of the methods, but all methods were found to lack precision. All methods also exhibited bias, as demonstrated by overprediction of the free concentration; however, none of the methods exhibited bias when the difference between the in vitro temperature of 25 degrees C and the in vivo temperature of 37 degrees C was considered. Because of their poor precision, the three methods evaluated in this study are not recommended for predicting free phenytoin concentration.