Variability of Phenytoin Protein Binding in Epilepsy

To the Editor.  —A number of problems arise from the study of DeMonaco and Lawless.¹ Blood samples for measurement of free phenytoin levels were drawn into heparinized tubes. This practice may introduce a major flaw in the estimation of free drug levels,^2,3 accounting for the discrepancy between predicted and measured free phenytoin concentrations. Lunde et al⁴ showed the importance of measuring free phenytoin concentrations at 37 °C; however, they did not indicate the temperature at which ultrafiltration was performed. DeMonaco and Lawless did not mention whether samples were taken from patients in the fasting state, as endogenous free fatty acids may displace phenytoin from binding sites.³ The authors also failed to provide precise data for the measurement of free phenytoin levels with the enzyme-multiplied immunoassay technique (EMIT) using the modified dilution procedure.The authors concluded that free phenytoin concentrations provide a more appropriate guide to monitoring