EFFECTS OF FELBAMATE ON THE PHARMACOKINETICS OF THE MONOHYDROXY AND DIHYDROXY METABOLITES OF OXCARBAZEPINE

The effects of felbamate on the multiple dose pharmacokinetics of the monohydroxy and dihydroxy metabolites of oxcarbazepine were assessed i n a placebo-controlled, randomized, double-blind crossover study in 18 healthy male volunteers. Oxcarbazepine, 1200 mg/day, was administered on an open basis in combination with double-blind placebo or 2400 mg/ day felbamate for two 10-day treatment periods separated by a 14-day w ashout period, Pharmacokinetic parameters of monohydroxyoxcarbazepine and dihydroxyoxcarbazepine were determined from plasma and urine sampl es obtained on the tenth day of each treatment period, Felbamate had n o effect on monohydroxyoxcarbazepine plasma or urine pharmacokinetics compared with placebo, but it significantly increased values for dihyd roxyoxcarbazepine maximum concentration and area under the curve from 0 to 12 hours, as well as urinary excretion of free and total dihydrox yoxcarbazepine. The mechanism that may account for the observations is the induction of oxidative metabolism of monohydroxyoxcarbazepine. De spite these changes, the relative amount of dihydroxyoxcarbazepine is small in comparison to monohydroxyoxcarbazepine, and antiepileptic act ivity is associated with monohydroxyoxcarbazepine rather than dihydrox yoxcarbazepine. Therefore we conclude that felbamate has no clinically relevant effects on the pharmacokinetics of oxcarbazepine in humans.