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• W2783246707 abstract "1. Itraconazole (ITZ), an antifungal azole derivate is a chiral drug that consists of four cis-diastereoisomers ((+)-2R,4S,2′R-ITZ-A; (+)-2R,4S,2′S-ITZ-B; (–)-2S,4R,2′S-ITZ-C and (–)-2S,4R,2′R-ITZ-D) which may differ in their pharmacokinetics and pharmacodynamics.2. As ITZ is known as a CYP3A4 inhibitor causing severe drug–drug interaction, the inhibitory potencies of its individual optical isomers towards nine drug-metabolising cytochrome P450 (including CYP3A, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1), were investigated.3. All ITZ diastereoisomers dose-dependently inhibited CYP3A activity in both used assays, midazolam and testosterone hydroxylation. The Ki values were assessed: for testosterone ITZ-A/0.085 µM; ITZ-B/0.91 µM, ITZ-C/0.20 µM and ITZ-D/0.022 µM; for midazolam ITZ-A/0.44 µM; ITZ-B/0.48 µM, ITZ-C/1.56 µM and ITZ-D/3.48 µM. The enzyme activity of CYP2C19 was moderately inhibited (IC50 30–53 µM), but in this case without large differences between the individual optical isomers.4. The significant differences between diastereoisomers were presented. Antifungal potency of ITZ stereoisomers also differs so the potential enantiopure preparations of ITZ was not of interest." @default.
• W2783246707 created "2018-01-26" @default.
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• W2783246707 date "2018-01-22" @default.
• W2783246707 modified "2023-09-25" @default.
• W2783246707 title "<i>In vitro</i> analysis of itraconazole cis-diastereoisomers inhibition of nine cytochrome P450 enzymes: stereoselective inhibition of CYP3A" @default.
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• W2783246707 doi "https://doi.org/10.1080/00498254.2018.1425510" @default.
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