Variability of phenytoin protein binding in epileptic patients

The variability of protein binding of phenytoin in epileptic patients was evaluated using a rapid ultrafiltration system. Thirty-one pairs of total and free (unbound) phenytoin plasma concentrations were reviewed. Filtered plasma for free phenytoin determination was obtained using an ultrafiltration membrane system. All samples were analyzed by an enzyme-multiplied immunoassay technique. A good correlation was obtained for total phenytoin concentration v free phenytoin concentration. Comparison of obtained and predicted free phenytoin values differed significantly. Of nine patients demonstrating toxic effects, six had total phenytoin concentrations within the accepted therapeutic range with free concentrations above the therapeutic range. The results of this study indicate a wide variation of phenytoin protein binding in chronic epileptic patients, implying that total phenytoin concentration must be interpreted cautiously, and use of free phenytoin concentration appears to be a more appropriate guide to therapy. The availability of a rapid method of ultrafiltration makes free phenytoin plasma levels readily available to the clinician.