Effect of felbamate on carbamazepine and its major metabolites

Mary L. Wagner, Rory P. Remmel, Nina M. Graves, Ilo E. Leppik

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51 Scopus citations


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 µg/ml during placebo or baseline periods to 2.4 µg/ml during felbamate treatment (p < 0.05); there was no significant change in diol concentrations. Mean carbamazepine concentrations decreased from 7.5 µg/ml during placebo treatment to 6.1 µg/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. Clinical Pharmacology and Therapeutics (1993) 53, 536–543; doi:

Original languageEnglish (US)
Pages (from-to)536-543
Number of pages8
JournalClinical Pharmacology & Therapeutics
Issue number5
StatePublished - May 1993


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