Study of inhibition of CYP2A6 by some drugs derived from quinoline
Identifieur interne : 002062 ( Main/Exploration ); précédent : 002061; suivant : 002063Study of inhibition of CYP2A6 by some drugs derived from quinoline
Auteurs : Yoshie Hirano [Japon] ; Takaharu Mizutani [Japon]Source :
- Journal of Pharmacy and Pharmacology [ 0022-3573 ] ; 2003-12.
English descriptors
- Teeft :
- Amino acids, Bovine, Bovine liver microsomes, Bovine microsomes, Chloroquine, Coumarin, Coumarin activity, Cyp2a, Cyp2a subfamily, Cytochrome, Derivative, Drug metab, High dose, Hirano, Human liver microsomes, Inhibition, Liver microsomes, Microsome, Mizutani, Monoclonal antibody, Norfloxacin, Peptide, Quinidine, Quinine, Quinoline, Quinoline derivatives, Rebamipide, Residues binding, Takaharu mizutani, Yoshie hirano.
Abstract
CYP2A6 metabolizes coumarin to 7‐hydroxycoumarin showing fluorescence, as measured by fluorometry. Firstly, we measured the inhibition of coumarin 7‐hydroxylase of cDNA‐expressed human CYP2A6 and in bovine liver microsomes, by quinoline and fluoroquinolines (FQ). Quinoline, 5‐FQ, 6‐FQ and 8‐FQ inhibited activity but 3‐FQ showed little inhibition. This suggests that the position 3 of quinoline is a recognition site for CYP2A6. We found similar patterns of coumarin 7‐hydroxylase activity with human pooled liver microsomes. The level of CYP2A6 in human and bovine microsomes is the same as that detected by immunological titration with monoclonal antibody against CYP2A6. Secondly, we studied the inhibition of CYP2A6 with clinically used drugs of quinoline compounds, such as norfloxacin as an antibacterial agent, quinidine as an antiarrhythmic agent, quinine and chloroquine as antimalaria agents and rebamipide as an anti‐ulcer agent. IC50 values (concentration producing 50% inhibition in activity) of norfloxacin, rebamipide and chloroquine at mm concentrations showed them to possess almost no inhibitory activity or influence on drug interaction. Meanwhile, the IC50 value of quinidine was 1.12 mm. The IC50 value of quinine was 160 μm with weak inhibition, suggesting that quinine, at a high dose, influences the metabolism of substrates for CYP2A6 by drug–drug interaction. These results also show that CYP2A6 discriminates the structure difference between the diastereoisomers quinidine and quinine.
Url:
DOI: 10.1211/0022357022278
Affiliations:
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Study of inhibition of CYP2A6 by some drugs derived from quinoline</title><author><name sortKey="Hirano, Yoshie" sort="Hirano, Yoshie" uniqKey="Hirano Y" first="Yoshie" last="Hirano">Yoshie Hirano</name></author><author><name sortKey="Mizutani, Takaharu" sort="Mizutani, Takaharu" uniqKey="Mizutani T" first="Takaharu" last="Mizutani">Takaharu Mizutani</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:5F12E3BB4DE4EA6994D17FBA892130A6254D61D5</idno><date when="2003" year="2003">2003</date><idno type="doi">10.1211/0022357022278</idno><idno type="url">https://api.istex.fr/ark:/67375/WNG-91H58K1Q-P/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">000686</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000686</idno><idno type="wicri:Area/Istex/Curation">000686</idno><idno type="wicri:Area/Istex/Checkpoint">000E97</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">000E97</idno><idno type="wicri:doubleKey">0022-3573:2003:Hirano Y:study:of:inhibition</idno><idno type="wicri:Area/Main/Merge">002080</idno><idno type="wicri:Area/Main/Curation">002062</idno><idno type="wicri:Area/Main/Exploration">002062</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main">Study of inhibition of CYP2A6 by some drugs derived from quinoline</title><author><name sortKey="Hirano, Yoshie" sort="Hirano, Yoshie" uniqKey="Hirano Y" first="Yoshie" last="Hirano">Yoshie Hirano</name><affiliation wicri:level="1"><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Drug Metabolism and Disposition, Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho‐ku, Nagoya 467–8603</wicri:regionArea><wicri:noRegion>Nagoya 467–8603</wicri:noRegion></affiliation></author><author><name sortKey="Mizutani, Takaharu" sort="Mizutani, Takaharu" uniqKey="Mizutani T" first="Takaharu" last="Mizutani">Takaharu Mizutani</name><affiliation wicri:level="1"><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Drug Metabolism and Disposition, Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho‐ku, Nagoya 467–8603</wicri:regionArea><wicri:noRegion>Nagoya 467–8603</wicri:noRegion></affiliation><affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Journal of Pharmacy and Pharmacology</title><title level="j" type="alt">JOURNAL OF PHARMACY AND PHARMACOLOGY</title><idno type="ISSN">0022-3573</idno><idno type="eISSN">2042-7158</idno><imprint><biblScope unit="vol">55</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="1667">1667</biblScope><biblScope unit="page" to="1672">1672</biblScope><biblScope unit="page-count">6</biblScope><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2003-12">2003-12</date></imprint><idno type="ISSN">0022-3573</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-3573</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Amino acids</term><term>Bovine</term><term>Bovine liver microsomes</term><term>Bovine microsomes</term><term>Chloroquine</term><term>Coumarin</term><term>Coumarin activity</term><term>Cyp2a</term><term>Cyp2a subfamily</term><term>Cytochrome</term><term>Derivative</term><term>Drug metab</term><term>High dose</term><term>Hirano</term><term>Human liver microsomes</term><term>Inhibition</term><term>Liver microsomes</term><term>Microsome</term><term>Mizutani</term><term>Monoclonal antibody</term><term>Norfloxacin</term><term>Peptide</term><term>Quinidine</term><term>Quinine</term><term>Quinoline</term><term>Quinoline derivatives</term><term>Rebamipide</term><term>Residues binding</term><term>Takaharu mizutani</term><term>Yoshie hirano</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">CYP2A6 metabolizes coumarin to 7‐hydroxycoumarin showing fluorescence, as measured by fluorometry. Firstly, we measured the inhibition of coumarin 7‐hydroxylase of cDNA‐expressed human CYP2A6 and in bovine liver microsomes, by quinoline and fluoroquinolines (FQ). Quinoline, 5‐FQ, 6‐FQ and 8‐FQ inhibited activity but 3‐FQ showed little inhibition. This suggests that the position 3 of quinoline is a recognition site for CYP2A6. We found similar patterns of coumarin 7‐hydroxylase activity with human pooled liver microsomes. The level of CYP2A6 in human and bovine microsomes is the same as that detected by immunological titration with monoclonal antibody against CYP2A6. Secondly, we studied the inhibition of CYP2A6 with clinically used drugs of quinoline compounds, such as norfloxacin as an antibacterial agent, quinidine as an antiarrhythmic agent, quinine and chloroquine as antimalaria agents and rebamipide as an anti‐ulcer agent. IC50 values (concentration producing 50% inhibition in activity) of norfloxacin, rebamipide and chloroquine at mm concentrations showed them to possess almost no inhibitory activity or influence on drug interaction. Meanwhile, the IC50 value of quinidine was 1.12 mm. The IC50 value of quinine was 160 μm with weak inhibition, suggesting that quinine, at a high dose, influences the metabolism of substrates for CYP2A6 by drug–drug interaction. These results also show that CYP2A6 discriminates the structure difference between the diastereoisomers quinidine and quinine.</div></front></TEI><affiliations><list><country><li>Japon</li></country></list><tree><country name="Japon"><noRegion><name sortKey="Hirano, Yoshie" sort="Hirano, Yoshie" uniqKey="Hirano Y" first="Yoshie" last="Hirano">Yoshie Hirano</name></noRegion><name sortKey="Mizutani, Takaharu" sort="Mizutani, Takaharu" uniqKey="Mizutani T" first="Takaharu" last="Mizutani">Takaharu Mizutani</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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