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Application of micellar electrokinetic capillary chromatography for evaluation of inhibitory effects on cytochrome P450 reaction
J Konecny, I Micikova, R Reminek, Z Glatz
Jazyk angličtina Země Nizozemsko
- MeSH
- aromatické hydroxylasy antagonisté a inhibitory chemie MeSH
- chromatografie micelární elektrokinetická kapilární metody MeSH
- diklofenak farmakologie chemie MeSH
- financování organizované MeSH
- inhibitory cytochromu P450 MeSH
- ketokonazol farmakologie chemie MeSH
- lidé MeSH
- molekulární struktura MeSH
- reprodukovatelnost výsledků MeSH
- sulfafenazol farmakologie chemie MeSH
- systém (enzymů) cytochromů P-450 chemie MeSH
- Check Tag
- lidé MeSH
The major aim of this work is to demonstrate the applicability of micellar electrokinetic capillary chromatography with SDS based pseudostationary phase for the screening of cytochrome P450 inhibitors. In contrast with the other capillary electrophoresis modes the cytochrome P450 reaction mixture thus could be used for the analysis without any pre-treatment. Cytochrome P450 2C9, one of the most important isoforms in human liver, was chosen as a model example for this study in combination with diclofenac as a probe substrate. The inhibitory effect on the given cytochrome P450 reaction was evaluated for two inhibitors with different inhibition potential - strong inhibitor sulfaphenazole and moderate inhibitor ketoconazole. As a result 50% inhibitory concentrations IC(50) and inhibition constants K(i) were evaluated; their values for both inhibitors were in a good agreement with the literature data determined by different methods.
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- $a Application of micellar electrokinetic capillary chromatography for evaluation of inhibitory effects on cytochrome P450 reaction / $c J Konecny, I Micikova, R Reminek, Z Glatz
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- $a Department of Biochemistry, Faculty of Science, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic.
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- $a The major aim of this work is to demonstrate the applicability of micellar electrokinetic capillary chromatography with SDS based pseudostationary phase for the screening of cytochrome P450 inhibitors. In contrast with the other capillary electrophoresis modes the cytochrome P450 reaction mixture thus could be used for the analysis without any pre-treatment. Cytochrome P450 2C9, one of the most important isoforms in human liver, was chosen as a model example for this study in combination with diclofenac as a probe substrate. The inhibitory effect on the given cytochrome P450 reaction was evaluated for two inhibitors with different inhibition potential - strong inhibitor sulfaphenazole and moderate inhibitor ketoconazole. As a result 50% inhibitory concentrations IC(50) and inhibition constants K(i) were evaluated; their values for both inhibitors were in a good agreement with the literature data determined by different methods.
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