{"_buckets": {"deposit": "3c6b55a3-b737-4d50-977d-46d649283ff5"}, "_deposit": {"id": "20095", "owners": [], "pid": {"revision_id": 0, "type": "depid", "value": "20095"}, "status": "published"}, "_oai": {"id": "oai:soar-ir.repo.nii.ac.jp:00020095", "sets": ["883"]}, "author_link": ["106292", "106293", "106294", "106295", "106296", "106297"], "item_1628147817048": {"attribute_name": "出版タイプ", "attribute_value_mlt": [{"subitem_version_resource": "http://purl.org/coar/version/c_970fb48d4fbd8a85", "subitem_version_type": "VoR"}]}, "item_6_biblio_info_6": {"attribute_name": "書誌情報", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2015-03-01", "bibliographicIssueDateType": "Issued"}, "bibliographicIssueNumber": "3", "bibliographicPageEnd": "447", "bibliographicPageStart": "441", "bibliographicVolumeNumber": "38", "bibliographic_titles": [{"bibliographic_title": "BIOLOGICAL \u0026 PHARMACEUTICAL BULLETIN"}]}]}, "item_6_description_20": {"attribute_name": "抄録", "attribute_value_mlt": [{"subitem_description": "Iguratimod is a novel disease-modifying antirheumatic drug. A blue letter (safety advisory) for drug interaction between iguratimod and warfarin was issued by the Ministry of Health, Labour and Welfare of Japan in May 2013. Iguratimod may affect warfarin metabolism catalyzed by CYP. However, it is not clear whether iguratimod inhibits warfarin oxidation. This study was performed to investigate the effects of iguratimod on warfarin 7-hydroxylation with human liver microsomes (HLMs) and recombinant CYP enzymes. Iguratimod concentration-dependently inhibited R,S-warfarin 7-hydroxylase activity of HLMs with an IC50 value of 15.2 µM. The inhibitory effect was examined with S-warfarin and R-warfarin to determine which enantiomer was more potently inhibited by iguratimod. Iguratimod potently inhibited the S-warfarin 7-hydroxylase activity of HLMs with an IC50 value of 14.1 µM, but showed only slight inhibition of R-warfarin 7-hydroxylation. Furthermore, iguratimod inhibited the S-warfarin 7-hydroxylase activity of recombinant CYP2C9.1 (rCYP2C9.1) and rCYP2C9.3 in a concentration-dependent manner with IC50 values of 10.8 and 20.1 µM, respectively. Kinetic analysis of the inhibition of S-warfarin 7-hydroxylation by iguratimod indicated competitive-type inhibition for HLMs and rCYP2C9.1 but mixed-type inhibition for rCYP2C9.3. The Ki values for HLMs, rCYP2C9.1, and rCYP2C9.3 were 6.74, 4.23, and 14.2 µM, respectively. Iguratimod did not exert metabolism-dependent inhibition of S-warfarin 7-hydroxylation. These results indicated that iguratimod is a potent direct inhibitor of CYP2C9-mediated warfarin 7-hydroxylation and that its inhibitory effect on CYP2C9.1 was more sensitive than that on CYP2C9.3.", "subitem_description_type": "Abstract"}]}, "item_6_description_30": {"attribute_name": "資源タイプ（コンテンツの種類）", "attribute_value_mlt": [{"subitem_description": "Article", "subitem_description_type": "Other"}]}, "item_6_description_5": {"attribute_name": "引用", "attribute_value_mlt": [{"subitem_description": "BIOLOGICAL \u0026 PHARMACEUTICAL BULLETIN.38(3):441-447(2015)", "subitem_description_type": "Other"}]}, "item_6_link_3": {"attribute_name": "信州大学研究者総覧へのリンク", "attribute_value_mlt": [{"subitem_link_text": "Yamaori, Satoshi", "subitem_link_url": "https://soar-rd.shinshu-u.ac.jp/profile/ja.jefNgUkh.html"}]}, "item_6_link_67": {"attribute_name": "WoS", "attribute_value_mlt": [{"subitem_link_text": "Web of Science", "subitem_link_url": "http://gateway.isiknowledge.com/gateway/Gateway.cgi?\u0026GWVersion=2\u0026SrcAuth=ShinshuUniv\u0026SrcApp=ShinshuUniv\u0026DestLinkType=FullRecord\u0026DestApp=WOS\u0026KeyUT=000350092300013"}]}, "item_6_publisher_4": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "PHARMACEUTICAL SOC JAPAN"}]}, "item_6_relation_47": {"attribute_name": "PubMed", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "25757926"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://www.ncbi.nlm.nih.gov/pubmed/25757926", "subitem_relation_type_select": "PMID"}}]}, "item_6_relation_48": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "10.1248/bpb.b14-00711"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://doi.org/10.1248/bpb.b14-00711", "subitem_relation_type_select": "DOI"}}]}, "item_6_rights_62": {"attribute_name": "権利", "attribute_value_mlt": [{"subitem_rights": "© 2015 The Pharmaceutical Society of Japan"}]}, "item_6_select_64": {"attribute_name": "著者版フラグ", "attribute_value_mlt": [{"subitem_select_item": "publisher"}]}, "item_6_source_id_35": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "0918-6158", "subitem_source_identifier_type": "PISSN"}]}, "item_6_source_id_39": {"attribute_name": "NII ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "0918-6158", "subitem_source_identifier_type": "PISSN"}]}, "item_6_source_id_40": {"attribute_name": "書誌レコードID", "attribute_value_mlt": [{"subitem_source_identifier": "AA11696048", "subitem_source_identifier_type": "NCID"}]}, "item_6_text_69": {"attribute_name": "wosonly authkey", "attribute_value_mlt": [{"subitem_text_value": "iguratimod; warfarin; CYP2C9; inhibition; drug-drug interaction; polymorphism"}]}, "item_6_text_70": {"attribute_name": "wosonly keywords", "attribute_value_mlt": [{"subitem_text_value": "ACTIVE RHEUMATOID-ARTHRITIS; PLACEBO-CONTROLLED TRIAL; DRUG-DRUG INTERACTIONS; DOUBLE-BLIND; CYP2C9; METHOTREXATE; PREDICTION; P-4502C9; THERAPY"}]}, "item_6_textarea_68": {"attribute_name": "wosonly abstract", "attribute_value_mlt": [{"subitem_textarea_value": "Iguratimod is a novel disease-modifying antirheumatic drug. A blue letter (safety advisory) for drug interaction between iguratimod and warfarin was issued by the Ministry of Health, Labour and Welfare of Japan in May 2013. Iguratimod may affect warfarin metabolism catalyzed by CYP. However, it is not clear whether iguratimod inhibits warfarin oxidation. This study was performed to investigate the effects of iguratimod on warfarin 7-hydroxylation with human liver microsomes (HLMs) and recombinant CYP enzymes. Iguratimod concentration-dependently inhibited R,S-warfarin 7-hydroxylase activity of HLMs with an IC50 value of 15.2 mu M. The inhibitory effect was examined with S-warfarin and R-warfarin to determine which enantiomer was more potently inhibited by iguratimod. Iguratimod potently inhibited the S-warfarin 7-hydroxylase activity of HLMs with an IC50 value of 14.1 mu M, but showed only slight inhibition of R-warfarin 7-hydroxylation. Furthermore, iguratimod inhibited the S-warfarin 7-hydroxylase activity of recombinant CYP2C9.1 (rCYP2C9.1) and rCYP2C9.3 in a concentration-dependent manner with IC50 values of 10.8 and 20.1 mu M, respectively. Kinetic analysis of the inhibition of S-warfarin 7-hydroxylation by iguratimod indicated competitive-type inhibition for HLMs and rCYP2C9.1 but mixed-type inhibition for rCYP2C9.3. The K-i values for HLMs, rCYP2C9.1, and rCYP2C9.3 were 6.74, 4.23, and 14.2 mu M, respectively. Iguratimod did not exert metabolism-dependent inhibition of S-warfarin 7-hydroxylation. These results indicated that iguratimod is a potent direct inhibitor of CYP2C9-mediated warfarin 7-hydroxylation and that its inhibitory effect on CYP2C9.1 was more sensitive than that on CYP2C9.3."}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Yamaori, S", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106292", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Takami, K", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106293", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Shiozawa, A", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106294", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Sakuyama, K", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106295", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Matsuzawa, N", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106296", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Ohmori, S", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106297", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2018-09-13"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "25460167_03.pdf", "filesize": [{"value": "738.6 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensefree": "© 2015 The Pharmaceutical Society of Japan", "licensetype": "license_note", "mimetype": "application/pdf", "size": 738600.0, "url": {"label": "25460167_03.pdf", "url": "https://soar-ir.repo.nii.ac.jp/record/20095/files/25460167_03.pdf"}, "version_id": "b5983d4a-f6e0-4566-8d40-7110e172b973"}]}, "item_keyword": {"attribute_name": "キーワード", "attribute_value_mlt": [{"subitem_subject": "iguratimod", "subitem_subject_scheme": "Other"}, {"subitem_subject": "warfarin", "subitem_subject_scheme": "Other"}, {"subitem_subject": "CYP2C9", "subitem_subject_scheme": "Other"}, {"subitem_subject": "inhibition", "subitem_subject_scheme": "Other"}, {"subitem_subject": "drug–drug interaction", "subitem_subject_scheme": "Other"}, {"subitem_subject": "polymorphism", "subitem_subject_scheme": "Other"}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "journal article", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "In Vitro Inhibition of CYP2C9-Mediated Warfarin 7-Hydroxylation by Iguratimod: Possible Mechanism of Iguratimod-Warfarin Interaction", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "In Vitro Inhibition of CYP2C9-Mediated Warfarin 7-Hydroxylation by Iguratimod: Possible Mechanism of Iguratimod-Warfarin Interaction", "subitem_title_language": "en"}]}, "item_type_id": "6", "owner": "1", "path": ["883"], "permalink_uri": "http://hdl.handle.net/10091/00020856", "pubdate": {"attribute_name": "PubDate", "attribute_value": "2018-09-13"}, "publish_date": "2018-09-13", "publish_status": "0", "recid": "20095", "relation": {}, "relation_version_is_last": true, "title": ["In Vitro Inhibition of CYP2C9-Mediated Warfarin 7-Hydroxylation by Iguratimod: Possible Mechanism of Iguratimod-Warfarin Interaction"], "weko_shared_id": -1}