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Carbamazepine and oxcarbazepine decrease phenytoin metabolism through inhibition of CYP2C19
F Lakehal1, C J Wurden, T F Kalhorn
1Department of Pharmaceutics, University of Washington, Seattle, WA 98195-7610, USA.
Epilepsy Research
|November 30, 2002
Summary
Carbamazepine (CBZ) and oxcarbazepine (OXC) metabolites inhibit CYP2C19, potentially increasing phenytoin levels. Caution is advised when co-administering these drugs with narrow therapeutic index medications.
Area of Science:
- Pharmacology
- Drug Metabolism
- Medicinal Chemistry
Background:
- Phenytoin levels can increase with carbamazepine (CBZ) co-medication.
- Understanding the mechanism of drug-drug interactions is crucial for patient safety.
Purpose of the Study:
- To investigate if carbamazepine (CBZ) and its metabolite (CBZE) inhibit CYP2C19-mediated phenytoin metabolism.
- To evaluate the inhibitory effects of oxcarbazepine (OXC) and its metabolite (MHD) on CYP2C19.
Main Methods:
- Utilized human liver microsomes to study drug metabolism.
- Employed cDNA-expressed CYP2C19 to assess specific enzyme inhibition.
- Measured the impact of CBZ, CBZE, OXC, and MHD on phenytoin metabolism.
Main Results:
- Carbamazepine (CBZ) and its metabolite (MHD) demonstrated inhibition of CYP2C19-mediated phenytoin metabolism.
- Inhibition occurred at therapeutic concentrations of CBZ and MHD.
- CBZE did not significantly inhibit CYP2C19-mediated phenytoin metabolism.
Conclusions:
- CBZ and OXC, through their metabolites, can inhibit CYP2C19.
- Co-administration of CBZ or OXC with CYP2C19 substrates requires caution due to potential drug interactions.
- This interaction may lead to altered therapeutic efficacy or toxicity of co-administered drugs.