title: Angiotensin II Receptor Blockers Inhibit the Generation of Epoxyeicosatrienoic Acid from Arachidonic Acid in Recombinant CYP2C9, CYP2J2 and Human Liver Microsomes.
abstract: Cytochrome P450 (CYP) 2C9, CYP2C8 and CYP2J2 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 (ARBs) may inhibit AA metabolism via CYP2C8. Using recombinant CYP2C9, CYP2J2 and human liver microsomes (HLMs), the aim was now to compare the ability of six different clinically used ARBs to inhibit AA metabolism in vitro. The rank order of the ARBs for the 50% inhibitory concentration (IC50) of AA metabolism was losartan <telmisartan <irbesartan <candesartan <olmesartan <valsartan via CYP2C9, and telmisartan <irbesartan <olmesartan <losartan <candesartan and valsartan via CYP2J2. The order for the HLMs was losartan <telmisartan <irbesartan <olmesartan <candesartan <valsartan. Some ARBs having lower concentration of IC50indicate that these ARBs might inhibit the AA metabolism in the liver.
authors.affiliation: Division of Clinical Pharmacology, Hokkaido Pharmaceutical University School of Pharmacy, Sapporo, Hokkaido, Japan.
authors.forename: Asuna
authors.initials: A
authors.lastname: Senda
authors.affiliation: Division of Clinical Pharmacology, Hokkaido Pharmaceutical University School of Pharmacy, Sapporo, Hokkaido, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mukai
authors.affiliation: Division of Pharmacotherapy, Hokkaido Pharmaceutical University School of Pharmacy, Sapporo, Hokkaido, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Hayakawa
authors.affiliation: Division of Clinical Pharmacology, Hokkaido Pharmaceutical University School of Pharmacy, Sapporo, Hokkaido, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Eliasson
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Rane
authors.affiliation: Division of Clinical Pharmacology, Hokkaido Pharmaceutical University School of Pharmacy, Sapporo, Hokkaido, Japan.
authors.forename: Takaki
authors.initials: T
authors.lastname: Toda
authors.affiliation: Division of Clinical Pharmacology, Hokkaido Pharmaceutical University School of Pharmacy, Sapporo, Hokkaido, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Inotsume
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism*; D065729:Cytochrome P-450 CYP2C9 / Q000378:metabolism*; D065688:Cytochrome P-450 CYP2C9 Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; C000717350:CYP2J2 protein, human; D065688:Cytochrome P-450 CYP2C9 Inhibitors; D011994:Recombinant Proteins; D016718:Arachidonic Acid; C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; C050715:8,9-epoxyeicosatrienoic acid; C046782:14,15-epoxy-5,8,11-eicosatrienoic acid; D003577:Cytochrome P-450 Enzyme System; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D000090762:Cytochrome P-450 CYP2J2; D015126:8,11,14-Eicosatrienoic Acid