Felbamate Increases Phenytoin but Decreases Carbamazepine Concentrations

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Abstract
Felbamate (FBM), a novel antiepleptic drug, was observed to have opposite effects on the serum concentrations of phenytoin (PHT) and carbamazepine (CBZ). Data from two male subjects who stabilized while they received both PHT and CBZ, with serum concentration fluctuations of <20 and 25%, respectively, form the basis of this report. Both patients, required a .gtoreq.20% reduction in PHT dose while receiving 38-40 mg/kg/day of FBM. When FBM was tapered to <20 mg/kg/day, a sudden drop in PHT concentrations occurred in both patients. As PHT concentrations rose, CBZ concentrations fell in both patients. The CBZ epoxide to parent ratios increased to 0.46 and 0.39, respectively during FBM treatment. The ratios were 0.18 in both patients when not receiving FBM. CBZ concentrations returned to baseline values after FBM was discontinued. This ususual and unexpected effect of FBM on two standard antiepileptic drugs underscores the need for evaluating pharmacokinetic interactions before major drug trials.