Binding parameters of phenytoin during monotherapy and polytherapy

The present in vivo study elucidated the effect of other commonly comedicated drugs on the phenytoin (PHT) Scatchard binding parameters. Specimens of 150 epileptic patients chronically treated with anticonvulsant drugs were analyzed. The results of covariance analysis suggest that phenobarbitone, ethosuximide, diazepam and folic acid do not alter binding of PHT to serum albumin. The contribution of carbamazepine and medazepam to the free fraction of PHT (decrease of about 0.4%) and/or Scatchard binding capacity (increase of about 1/3) is ambiguous and not statistically significant at the p less than 0.05 level. On the contrary, we found a statistically significant decrease of PHT binding in patients comedicated with valproic acid (VPA) and primidone (PRM). The decrease of about 25% in binding capacity evoked an increase of about 1% (VPA), and 1.5% (PRM), respectively in PHT free fraction.