Fenofibrate-induced decrease of expression of CYP2C11 and CYP2C6 in rat
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
21968795
DOI
10.1002/bdd.774
Knihovny.cz E-resources
- MeSH
- Aryl Hydrocarbon Hydroxylases biosynthesis MeSH
- Enzyme Repression MeSH
- Fenofibrate pharmacology MeSH
- Hypertriglyceridemia metabolism MeSH
- Hypolipidemic Agents pharmacology MeSH
- Microsomes, Liver drug effects metabolism MeSH
- Rats MeSH
- Rats, Wistar MeSH
- Cytochrome P450 Family 2 MeSH
- Steroid 16-alpha-Hydroxylase biosynthesis MeSH
- Steroid 21-Hydroxylase biosynthesis MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Aryl Hydrocarbon Hydroxylases MeSH
- CYP2C11 protein, rat MeSH Browser
- Cyp2c6v1 protein, rat MeSH Browser
- Fenofibrate MeSH
- Hypolipidemic Agents MeSH
- Cytochrome P450 Family 2 MeSH
- Steroid 16-alpha-Hydroxylase MeSH
- Steroid 21-Hydroxylase MeSH
This short communication is aimed to investigate whether the widely used hypolipidemic drug fenofibrate affects CYP2C11 and CYP2C6 in rats, both counterparts of human CYP2C9, known to metabolise many drugs including S-warfarin and largely used non-steroidal antiinflammatory drugs such as ibuprofen, diclofenac and others. The effects of fenofibrate on the expression of rat liver CYP2C11 and CYP2C6 were studied in both healthy Wistar rats and hereditary hypertriglyceridemic rats. Both strains of rats were fed on diet containing fenofibrate (0.1% w/w) for 20 days. Fenofibrate highly significantly suppressed the expression of mRNA of CYP2C11 and less that of CYP2C6 in liver microsomes of both rat strains; this effect was associated with a corresponding decrease in protein levels. The results indicate that the combination of fenofibrate with drugs metabolised by CYP2C9 in humans should be taken with caution as it may lead, for example, to the potentiation of warfarin effects. This type of drug interaction has been observed previously and the results presented here could contribute to the explanation of their mechanism.
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