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PubMed · 12458024

Carbamazepine and oxcarbazepine decrease phenytoin metabolism through inhibition of CYP2C19.

F Lakehal·C J Wurden·T F Kalhorn·R H Levy
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Abstract

Multiple studies suggest that phenytoin concentrations increase with CBZ co-medication. This study evaluated the hypothesis that CBZ and/or its major metabolite (CBZE) inhibit CYP2C19-mediated phenytoin metabolism using human liver microsomes and cDNA-expressed CYP2C19. Oxcarbazepine (OXC), and its 10-monohydroxy metabolite (MHD) were also evaluated. CBZ and MHD inhibited CYP2C19-mediated phenytoin metabolism at therapeutic concentrations. Thus, administration of CBZ and OXC with CYP2C19 substrates with narrow therapeutic ranges should be done cautiously.

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AnticonvulsantsAryl Hydrocarbon HydroxylasesCarbamazepineChlorophyllCytochrome P-450 CYP2C19Dose-Response Relationship, DrugDrug InteractionsEnzyme InhibitorsHumansIn Vitro TechniquesLiverMephenytoinMicrosomesMixed Function OxygenasesOxcarbazepinePhenytoinRecombinant ProteinsComparative StudyJournal ArticleResearch Support, U.S. Gov't, P.H.S.

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F Lakehal, C J Wurden, T F Kalhorn, R H Levy. 2002. Carbamazepine and oxcarbazepine decrease phenytoin metabolism through inhibition of CYP2C19.. https://doi.org/10.1016/s0920-1211(02)00188-2

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