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.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Anticonvulsants / metabolism*
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Anticonvulsants / pharmacology*
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Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors*
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Aryl Hydrocarbon Hydroxylases / metabolism
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Carbamazepine / analogs & derivatives*
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Carbamazepine / pharmacology*
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Chlorophyll / analogs & derivatives*
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Cytochrome P-450 CYP2C19
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Dose-Response Relationship, Drug
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Drug Interactions
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Enzyme Inhibitors / pharmacology*
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Humans
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In Vitro Techniques
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Liver / drug effects
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Liver / enzymology
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Liver / metabolism
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Mephenytoin / analogs & derivatives*
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Microsomes / drug effects
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Microsomes / enzymology
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Microsomes / metabolism
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Mixed Function Oxygenases / antagonists & inhibitors*
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Mixed Function Oxygenases / metabolism
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Oxcarbazepine
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Phenytoin / metabolism*
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Phenytoin / pharmacology
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / metabolism
Substances
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Anticonvulsants
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Enzyme Inhibitors
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Recombinant Proteins
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Chlorophyll
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2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a
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Carbamazepine
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Phenytoin
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4-hydroxymephenytoin
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Mixed Function Oxygenases
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Aryl Hydrocarbon Hydroxylases
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CYP2C19 protein, human
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Cytochrome P-450 CYP2C19
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Mephenytoin
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Oxcarbazepine