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• W2040260015 startingPage "615" @default.
• W2040260015 abstract "1. Cytochrome P450 enzyme system is the most important contributor to oxidative metabolism of drugs. Modification, and more specifically inhibition, of this system is an important determinant of several drug–drug interactions (DDIs).2. Effects of the antimalarial agent artemisinin and its structural analogues, artemether, artesunate and dihydroartemisinin, on seven of the major human liver CYP isoforms (CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6 and 3A4) were evaluated using recombinant enzymes (fluorometric assay) and human liver microsomes (LC–MS/MS analysis). Inhibitory potency (IC50) and mechanisms of inhibition were evaluated using nonlinear regression analysis. In vitro–in vivo extrapolation using the [I]/Ki ratio was applied to predict the risk of DDI in vivo.3. All compounds tested inhibited the enzymatic activity of CYPs, mostly through a mixed type of inhibition, with CYP1A2, 2B6, 2C19 and 3A4 being affected. A high risk of interaction in vivo was predicted if artemisinin is coadministrated with CYP1A2 or 2C19 substrates.4. With respect to CYP1A2 inhibition in vivo by artemisinin compounds, our findings are in line with previously published data. However, reported risks of interaction may be overpredicted and should be interpreted with caution." @default.
• W2040260015 created "2016-06-24" @default.
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• W2040260015 date "2014-01-08" @default.
• W2040260015 modified "2023-09-30" @default.
• W2040260015 title "Effects of artemisinin antimalarials on Cytochrome P450 enzymes<i>in vitro</i>using recombinant enzymes and human liver microsomes: potential implications for combination therapies" @default.
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• W2040260015 doi "https://doi.org/10.3109/00498254.2013.878815" @default.
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• W2040260015 hasPublicationYear "2014" @default.
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