Effect of felbamate on carbamazepine and its major metabolites

Felbamate is a novel antiepileptic drug that is now available in the United States. During a previous double-blind, crossover, placebo-controlled safety and efficacy study, concomitant phenytoin concentrations increased, whereas carbamazepine concentrations decreased. We evaluated the effect of felbamate on the concentrations of carbamazepine and of its major metabolites, carbamazepine-10,11-epoxide (epoxide) and carbamazepine-trans-10,11-diol (diol) in 26 patients. After the addition of felbamate, mean epoxide concentrations increased from 1.8 micrograms/ml during placebo or baseline periods to 2.4 micrograms/ml during felbamate treatment (p < 0.05); there was no significant change in diol concentrations. Mean carbamazepine concentrations decreased from 7.5 micrograms/ml during placebo treatment to 6.1 micrograms/ml during felbamate treatment (p < 0.05). Mechanisms that could account for the increase in steady-state epoxide concentrations are induction of carbamazepine metabolism to epoxide, inhibition of the conversion of epoxide to diol, or both.