Carbamazepine-phenytoin interaction: elevation of plasma phenytoin concentrations due to carbamazepine comedication

By intrapatient comparison at constant phenytoin (PHT) dose, the effect of carbamazepine (CBZ) comedication on PHT was studied in a group of 24 epileptic outpatients. In half of the patients with steady-state PHT plasma concentration, a significant increase of this concentration was noted after CBZ was added to their regimen. Twenty percent showed clinical manifestations of acute drug toxicity initially thought to be CBZ related. The mean PHT plasma concentration for the 12 patients (22.7 +/- 5.64 micrograms/ml) as well as concentration/dose ratio for PHT (4.61 +/- 1.65 micrograms/ml plasma per mg/kg/day dose) was significantly higher (p less than 0.001) with concomitant administration of CBZ than when PHT was given alone: PHT concentration, 12.54 +/- 3.93 micrograms/ml and PHT concentration/dose ratio, 2.52 +/- 0.78 micrograms/ml plasma per mg/kg/day dose. Those patients with higher PHT plasma concentrations seem to be at higher risk of PHT toxicity due to CBZ comedication.