Carbamazepine and oxcarbazepine decrease phenytoin metabolism through inhibition of CYP2C19

• Published in: Epilepsy research Vol. 52; no. 2; pp. 79 - 83
• Main Authors: Lakehal, F, Wurden, C.J, Kalhorn, T.F, Levy, R.H
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01-12-2002; Elsevier
• Subjects: Anticonvulsants - metabolism; Anticonvulsants - pharmacology; Anticonvulsants. Antiepileptics. Antiparkinson agents; Aryl Hydrocarbon Hydroxylases - antagonists & inhibitors; Aryl Hydrocarbon Hydroxylases - metabolism; Biological and medical sciences; Carbamazepine; Carbamazepine - analogs & derivatives; Carbamazepine - pharmacology; Chlorophyll - analogs & derivatives; Cytochrome P-450 CYP2C19; Cytochrome P450; Dose-Response Relationship, Drug; Drug interaction; Drug Interactions; Enzyme Inhibitors - pharmacology; Humans; In Vitro Techniques; Inhibition; Liver - drug effects; Liver - enzymology; Liver - metabolism; Medical sciences; Mephenytoin - analogs & derivatives; Microsomes - drug effects; Microsomes - enzymology; Microsomes - metabolism; Mixed Function Oxygenases - antagonists & inhibitors; Mixed Function Oxygenases - metabolism; Neuropharmacology; Oxcarbazepine; Pharmacology. Drug treatments; Phenytoin; Phenytoin - metabolism; Phenytoin - pharmacology; Recombinant Proteins - antagonists & inhibitors; Recombinant Proteins - metabolism; Oxcarbazepine; Drug interaction; Inhibition; Cytochrome P450; Carbamazepine; Phenytoin; Human; Digestive system; Liver; Tricyclic compound; Microsome; Metabolism; In vitro; Biological activity; Chemotherapy; Treatment; Dibenzazepine derivatives
• ISSN: 0920-1211; 1872-6844
• DOI: 10.1016/S0920-1211(02)00188-2

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.