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| rdf:type
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| Description
| - Warfarin, a known anticoagulant, was initially marketed as a rodenticide. Warfarin was found to be effective and relatively safe in prevention of thrombosis and embolism. Several forms of liver microsomal cytochrome P450 (CYP) are known to metabolize warfarin. Hydroxylation of warfarin in rats is mainly catalyzed by enzymes of CYP2C, CYP2B, CYPIA, and CYP3A subfamilies. Five primary metabolites were identified as 4'-hydroxywarfarin, 6-hydroxywarfarin, 7-hydroxywarfarin, 8 -hydroxywarfarin, and 1O-hydroxywarfarin. Inhibitory properties of silybin on 7-hydroxylation of warfarin (CYP2C9) using human liver microsomes and a recombinant CYP2C9 enzyme is known. Warfarin interactions lead to difficulties with titration of a right dose of this drug. A typical flavonolignan, silybin (main component of silymarin), was chosen in this study to evaluate its possible effect on warfarin metabolism in male rats in vitro. The HPLC method for determination of metabolism of warfarin in rats in vitro was introduced. Silybin has hepatoprotective properties and possibly is also a potential anticancer agent. Silybin was tested for its ability to inhibit the activities of human Iiver microsomal CYP. The results have shown the inhibition of activity of CYPlA2 (IC50 220 μM), CYP2CS (IC50 250 μM), CYP2C9 (IC50 50 μM) and CYP3A4 (IC50 34 μM). Results have shown that silybin does not prominently interfere with warfarin metabolism. In other words, it causes an inhibiton of formation of hydroxymetabolites of warfarin, e,g. 4' –hydroxywarfarin by 25% only, and 7-hydroxywarfarin by 20%. Silybin hence should be taken as a relatively safe drug whose metabolism does not interfere significantly with major CYP-catalyzed routes of warfarin biotransformation.
- Warfarin, a known anticoagulant, was initially marketed as a rodenticide. Warfarin was found to be effective and relatively safe in prevention of thrombosis and embolism. Several forms of liver microsomal cytochrome P450 (CYP) are known to metabolize warfarin. Hydroxylation of warfarin in rats is mainly catalyzed by enzymes of CYP2C, CYP2B, CYPIA, and CYP3A subfamilies. Five primary metabolites were identified as 4'-hydroxywarfarin, 6-hydroxywarfarin, 7-hydroxywarfarin, 8 -hydroxywarfarin, and 1O-hydroxywarfarin. Inhibitory properties of silybin on 7-hydroxylation of warfarin (CYP2C9) using human liver microsomes and a recombinant CYP2C9 enzyme is known. Warfarin interactions lead to difficulties with titration of a right dose of this drug. A typical flavonolignan, silybin (main component of silymarin), was chosen in this study to evaluate its possible effect on warfarin metabolism in male rats in vitro. The HPLC method for determination of metabolism of warfarin in rats in vitro was introduced. Silybin has hepatoprotective properties and possibly is also a potential anticancer agent. Silybin was tested for its ability to inhibit the activities of human Iiver microsomal CYP. The results have shown the inhibition of activity of CYPlA2 (IC50 220 μM), CYP2CS (IC50 250 μM), CYP2C9 (IC50 50 μM) and CYP3A4 (IC50 34 μM). Results have shown that silybin does not prominently interfere with warfarin metabolism. In other words, it causes an inhibiton of formation of hydroxymetabolites of warfarin, e,g. 4' –hydroxywarfarin by 25% only, and 7-hydroxywarfarin by 20%. Silybin hence should be taken as a relatively safe drug whose metabolism does not interfere significantly with major CYP-catalyzed routes of warfarin biotransformation. (en)
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| Title
| - Effect of model flavonolignan on metabolism of warfarin in rats in vitro
- Effect of model flavonolignan on metabolism of warfarin in rats in vitro (en)
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| skos:prefLabel
| - Effect of model flavonolignan on metabolism of warfarin in rats in vitro
- Effect of model flavonolignan on metabolism of warfarin in rats in vitro (en)
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| skos:notation
| - RIV/70883521:28110/11:43865998!RIV12-MSM-28110___
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| http://linked.open...avai/riv/aktivita
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| http://linked.open...avai/riv/aktivity
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| http://linked.open...iv/cisloPeriodika
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| http://linked.open...vai/riv/dodaniDat
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| http://linked.open...aciTvurceVysledku
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| http://linked.open.../riv/druhVysledku
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| http://linked.open...iv/duvernostUdaju
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| http://linked.open...titaPredkladatele
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| http://linked.open...dnocenehoVysledku
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| http://linked.open...ai/riv/idVysledku
| - RIV/70883521:28110/11:43865998
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| http://linked.open...riv/jazykVysledku
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| http://linked.open.../riv/klicovaSlova
| - warfarin, cytochrome P450, rat liver microsomes, silybin (en)
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| http://linked.open.../riv/klicoveSlovo
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| http://linked.open...odStatuVydavatele
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| http://linked.open...ontrolniKodProRIV
| |
| http://linked.open...i/riv/nazevZdroje
| - Interdisciplinary Toxicology
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| http://linked.open...in/vavai/riv/obor
| |
| http://linked.open...ichTvurcuVysledku
| |
| http://linked.open...cetTvurcuVysledku
| |
| http://linked.open...UplatneniVysledku
| |
| http://linked.open...v/svazekPeriodika
| |
| http://linked.open...iv/tvurceVysledku
| - Křen, Vladimír
- Anzenbacher, Pavel
- Anzenbacherová, Eva
- Jančová, Petra
- Tunková, Alena
|
| issn
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| number of pages
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| http://localhost/t...ganizacniJednotka
| |
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