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• W2051994187 endingPage "350" @default.
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• W2051994187 abstract "Cytochrome P450 2C9 (CYP2C9) is a polymorphic enzyme responsible for the metabolism of many important drugs, including diclofenac. CYP2C9*3 and CYP2C9* 13 are the principal variant alleles found in the Chinese population. CYP2C9*3 has been reported to reduce the metabolism of diclofenac and alter the extent of drug-drug interactions (DDIs). The effects of CYP2C9* 13 on diclofenac metabolism are not well studied, and the influences of CYP2C9* 13 on DDIs between diclofenac and clinical drugs are still unknown. In this study, CYP2C9.1 (the wildtype enzyme), CYP2C9.3 and CYP2C9.13 were expressed in yeast, and their metabolic kinetics for diclofenac 4′-hydroxylation were examined. From the in vitro data, we predicted a decrease in the ratio of diclofenac oral clearance (the ratio of oral clearance in subjects with variant CYP2C9 alleles to that in wildtype subjects (CLoralR)) in subjects carrying CYP2C9*3 or CYP2C9* 13 alleles. Furthermore, we investigated the effects of these two alleles on diclofenac-drug interactions. The potentials of nine clinically used drugs to inhibit diclofenac 4′-hydroxylation catalyzed by the alleles were compared. Our results indicated that CYP2C9.3 and CYP2C9.13 can alter the CYP-inhibitory potencies of some tested drugs. In particular, CYP2C9.13 significantly weakened the inhibitory potencies of sulfaphenazole, fluvastatin, fluvoxamine and tranylcypromine. These data provide helpful guidelines for co-administration of diclofenac with other drugs in individuals carrying CYP2C9*3 and CYP2C9* 13 alleles." @default.
• W2051994187 created "2016-06-24" @default.
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• W2051994187 date "2010-01-01" @default.
• W2051994187 modified "2023-10-18" @default.
• W2051994187 title "Effects of CYP2C9*3 and CYP2C9* 13 on Diclofenac Metabolism and Inhibition-based Drug-Drug Interactions" @default.
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• W2051994187 doi "https://doi.org/10.2133/dmpk.dmpk-10-rg-009" @default.
• W2051994187 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20814155" @default.
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