Angiotensin II Receptor Blockers Inhibit the Generation of Epoxyeicosatrienoic Acid from Arachidonic Acid in Recombinant CYP 2C9, CYP 2J2 and Human Liver Microsomes

Cytochrome P450 ( CYP ) 2C9, CYP 2C8 and CYP 2J2 enzymes, which metabolize arachidonic acid (AA) to epoxyeicosatrienoic acids, have cardioprotective effects including anti‐inflammation and vasodilation. We have recently shown that some angiotensin II receptor blockers ( ARB s) may inhibit AA metabol...

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Veröffentlicht in:Basic & clinical pharmacology & toxicology 2017-10, Vol.121 (4), p.239-245
Hauptverfasser: Senda, Asuna, Mukai, Yuji, Hayakawa, Toru, Kato, Yuka, Eliasson, Erik, Rane, Anders, Toda, Takaki, Inotsume, Nobuo
Format: Artikel
Sprache:eng
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Zusammenfassung:Cytochrome P450 ( CYP ) 2C9, CYP 2C8 and CYP 2J2 enzymes, which metabolize arachidonic acid (AA) to epoxyeicosatrienoic acids, have cardioprotective effects including anti‐inflammation and vasodilation. We have recently shown that some angiotensin II receptor blockers ( ARB s) may inhibit AA metabolism via CYP 2C8. Using recombinant CYP 2C9, CYP 2J2 and human liver microsomes ( HLM s), the aim was now to compare the ability of six different clinically used ARB s to inhibit AA metabolism in vitro . The rank order of the ARB s for the 50% inhibitory concentration ( IC 50 ) of AA metabolism was losartan
ISSN:1742-7835
1742-7843
DOI:10.1111/bcpt.12789