title: Fenofibrate-induced decrease of expression of CYP2C11 and CYP2C6 in rat.
abstract: 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.
authors.affiliation: Institute of Pharmacology, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská, 3, 775 15 Olomouc, Czech Republic.
authors.forename: Rostislav
authors.initials: R
authors.lastname: Večeřa
authors.forename: Alice
authors.initials: A
authors.lastname: Zachařová
authors.forename: Jan
authors.initials: J
authors.lastname: Orolin
authors.forename: Jan
authors.initials: J
authors.lastname: Strojil
authors.forename: Nina
authors.initials: N
authors.lastname: Skottová
authors.forename: Pavel
authors.initials: P
authors.lastname: Anzenbacher
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D000072467:Cytochrome P450 Family 2; D004794:Enzyme Repression; D011345:Fenofibrate / Q000494:pharmacology*; D015228:Hypertriglyceridemia / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D039181:Steroid 16-alpha-Hydroxylase / Q000096:biosynthesis*; D013255:Steroid 21-Hydroxylase / Q000096:biosynthesis*
chemical_list: D000960:Hypolipidemic Agents; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; C089877:Cyp2c6v1 protein, rat; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase; D013255:Steroid 21-Hydroxylase; D011345:Fenofibrate