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.
Wagner
M L
ML
College of Pharmacy, University of Minnesota, Minneapolis 55455.
Remmel
R P
RP
Graves
N M
NM
Leppik
I E
IE
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000031:analogs & derivatives / Q000097:blood*; D004311:Double-Blind Method; D004347:Drug Interactions; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy; D000078328:Felbamate; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D048448:Phenylcarbamates; D010672:Phenytoin / Q000097:blood; D011409:Propylene Glycols / Q000494:pharmacology*
D000927:Anticonvulsants; D048448:Phenylcarbamates; D011409:Propylene Glycols; D002220:Carbamazepine; C004822:10,11-dihydro-10,11-dihydroxy-5H-dibenzazepine-5-carboxamide; D010672:Phenytoin; C012227:carbamazepine epoxide; D000078328:Felbamate