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 in 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 washout period. Pharmacokinetic parameters of monohydroxyoxcarbazepine and dihydroxyoxcarbazepine were determined from plasma and urine samples obtained on the tenth day of each treatment period. Felbamate had no effect on monohydroxyoxcarbazepine plasma or urine pharmacokinetics compared with placebo, but it significantly increased values for dihydroxyoxcarbazepine maximum concentration and area under the curve from 0 to 12 hours, as well as urinary excretion of free and total dihydroxyoxcarbazepine. The mechanism that may account for the observations is the induction of oxidative metabolism of monohydroxyoxcarbazepine. Despite these changes, the relative amount of dihydroxyoxcarbazepine is small in comparison to monohydroxyoxcarbazepine, and antiepileptic activity is associated with monohydroxyoxcarbazepine rather than dihydroxyoxcarbazepine. Therefore we conclude that felbamate has no clinically relevant effects on the pharmacokinetics of oxcarbazepine in humans.
Hulsman
J A
JA
Epilepsiecentrum Kempenhaeghe, Heeze, The Netherlands.
Rentmeester
T W
TW
Banfield
C R
CR
Reidenberg
P
P
Colucci
R D
RD
Meehan
J W
JW
Radwanski
E
E
Mojaverian
P
P
Lin
C C
CC
Nezamis
J
J
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D000078328:Felbamate; D006801:Humans; D008297:Male; D000078330:Oxcarbazepine; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000494:pharmacology*
D000927:Anticonvulsants; D048448:Phenylcarbamates; D011409:Propylene Glycols; D002220:Carbamazepine; D000078330:Oxcarbazepine; D000078328:Felbamate