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• W1898202502 startingPage "1534" @default.
• W1898202502 abstract "Naftopidil (NAF) is a chiral compound with two enantiomers (R(+)-NAF and S(-)-NAF) and is used as a racemic mixture in clinical practice. This study aims to investigate the metabolism of NAF enantiomers in pooled human liver microsomes (HLMs) and cytochrome P450 isozymes (CYPs) involved in their metabolism.Metabolism studies were conducted in vitro using HLMs. Specific chemical inhibitors and recombinant human CYPs were used to confirm that the CYPs contributed to the metabolism of NAF enantiomers.Three metabolites were found and characterized in the HLMs incubations from R(+)-NAF and S(-)-NAF, respectively. The major metabolic pathways of R(+)-NAF and S(-)-NAF were demethylation and hydroxylation. CYP2C9 and CYP2C19 inhibitors strongly inhibited R(+)-NAF metabolism, and CYP1A2, CYP2C8, CYP2D6 and CYP3A4/5 inhibitors moderately inhibited R(+)-NAF metabolism. CYP2C9 inhibitors strongly inhibited S(-)-NAF metabolism, and CYP2C8, CYP2C19 and CYP3A4/5 inhibitors moderately inhibited S(-)-NAF metabolism. Consistent with the results of chemical inhibitors experiments, recombinant human CYP2C9 and CYP2C19 contributed greatly to R(+)-NAF metabolism, and CYP2C9 contributed greatly to S(-)-NAF metabolism.Both R(+)-NAF and S(-)-NAF are metabolized to three metabolites in HLMs. CYP2C9 plays the most important role in the demethylation and hydroxylation of both NAF enantiomers, CYP2C19 is another major CYP isoform that is involved in R(+)-NAF metabolism." @default.
• W1898202502 created "2016-06-24" @default.
• W1898202502 creator A5001994950 @default.
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• W1898202502 date "2014-06-19" @default.
• W1898202502 modified "2023-09-23" @default.
• W1898202502 title "Identification of human cytochrome P450 isozymes involved in the metabolism of naftopidil enantiomers <i>in vitro</i>" @default.
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• W1898202502 doi "https://doi.org/10.1111/jphp.12281" @default.
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