The Effect of Certain Drugs on the Plasma Protein Binding of Phenytoin

Summary: Most of the phenytoin in plasma is protein bound. Anti‐convulsants are often prescribed in combination and it is important to know if other anticonvulsants displace phenytoin from its plasma‐protein binding sites. If this happened, the biological effect of phenytoin could be altered without much change in its total concentration in plasma. The binding of phenytoin to serum albumin and plasma protein in vitro has been studied by ultrafiltration techniques and equilibrium dialysis at a variety of temperatures and in the presence of “therapeutic” concentrations of other anticonvulsants and aspirin. Equilibrium dialysis and ultrafiltration yielded comparable results. Phenytoin binding de‐creased with increasing temperature (92% bound at 3 °C, 80% bound at 37 °C). With the possible exception of sulthiame, the other anticonvulsants tested (phenobarbitone, ethosuximide, diazepam and carbamazepine), and also aspirin, did not displace phenytoin from its plasma protein binding sites. These findings may be helpful in interpreting plasma phenytoin concentrations when other anticonvulsants are prescribed simultaneously.