Variability of Phenytoin Protein Binding in Epilepsy-Reply

In Reply.  —The effect of heparinized collection tubes on the evaluation of free phenytoin levels has been of some controversy. Giacomini et al¹ showed variability in protein binding of phenytoin in patients receiving intravenously administered heparin sodium. Weigand et al² examined the effects of the addition of heparin to serum and concluded that this drug has no significant effect on the protein binding of phenytoin.Previous studies have noted variability in the results obtained in free drug determinations at different temperatures. We did not perform ultrafiltration at 37 °C for two reasons. First, it is technically more difficult, and second, results obtained at room temperature correlate well with those obtained with equilibrium dialysis at 37 °C.³ Ultrafiltration at 37 °C will provide higher values because of increased permeability of the membrane to serum proteins.³ All of our samples were filtered at room temperature, and all were collected with