{"created":"2024-03-15T03:11:30.570011+00:00","id":2001328,"links":{},"metadata":{"_buckets":{"deposit":"d03a8b44-f28f-4665-92ec-e9f4e0fcd0bd"},"_deposit":{"created_by":10,"id":"2001328","owners":[10],"pid":{"revision_id":0,"type":"depid","value":"2001328"},"status":"published"},"_oai":{"id":"oai:repository.lib.tottori-u.ac.jp:02001328","sets":["1:9","2:12","23:34:1710471377862:1710471383343"]},"author_link":["4867"],"item_10001_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2024-02-21","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"1","bibliographicNumberOfPages":"10","bibliographicPageEnd":"40","bibliographicPageStart":"31","bibliographicVolumeNumber":"67","bibliographic_titles":[{"bibliographic_title":"Yonago Acta Medica","bibliographic_titleLang":"en"}]}]},"item_10001_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Background: Voriconazole is an antifungal drug for which therapeutic monitoring is recommended to prevent side effects. Temporary administration of the antiemetic drug fosaprepitant remarkably decreases the plasma concentration of voriconazole from the therapeutic range. The ratio of the major metabolite voriconazole N-oxide to voriconazole exceeded that at any other time for a patient who started chemotherapy during voriconazole therapy. We attributed this unpredictable result to cytochrome P450 3A4 induced by aprepitant that was converted from fosaprepitant in vivo. Methods: Concentrations of voriconazole and voriconazole N-oxide were measured using liquid chromatography-mass spectrometry/mass spectrometry in primary human hepatocytes after incubation with aprepitant. Aprepitant suppressed voriconazole N-oxide formation within 24 h, followed by a continuous increase. Levels of drug-metabolizing cytochrome P450 mRNA were measured using real-time PCR in primary human hepatocytes incubated with aprepitant. Results: Cytochrome P450 3A4 and 2C9 mRNA levels increased ~4- and 2-fold, respectively, over time. Cytochrome P450 3A4 induction was confirmed using reporter assays. We also assessed L-755446, a major metabolite of aprepitant that lacks a triazole ring. Both compounds dose-dependently increased reporter activity; however, induction by L-755446 was stronger than that by aprepitant. Conclusion: These results indicate that aprepitant initially inhibited voriconazole metabolism via its triazole ring and increased cytochrome P450 3A4 induction following L-755446 formation. The decrease in plasma voriconazole concentration 7 days after fosaprepitant administration was mainly attributed to cytochrome P450 3A4 induction by L-755446.","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Tottori University Medical Press","subitem_publisher_language":"en"}]},"item_10001_relation_16":{"attribute_name":"情報源","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"Yonago Acta Medica. 2024, 67(1), 31-40."}]}]},"item_10001_relation_17":{"attribute_name":"関連サイト","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://www.lib.tottori-u.ac.jp/yam/yam/yam67-1/67-1contents.html"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://www.lib.tottori-u.ac.jp/yam/yam/yam67-1/67-1contents.html","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://doi.org/10.33160/yam.2024.02.004"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.33160/yam.2024.02.004","subitem_relation_type_select":"DOI"}}]},"item_10001_rights_15":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"(C)2024 Tottori University Medical Press","subitem_rights_language":"en"}]},"item_10001_source_id_11":{"attribute_name":"書誌レコードID","attribute_value_mlt":[{"subitem_source_identifier":"AA00892882","subitem_source_identifier_type":"NCID"}]},"item_10001_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"13468049","subitem_source_identifier_type":"PISSN"}]},"item_10001_text_33":{"attribute_name":"著者所属（英）","attribute_value_mlt":[{"subitem_text_value":"Department of Pharmacy, Tottori University Hospital"},{"subitem_text_value":"Laboratory of Environmental and Health Sciences, Tohoku Medical and Pharmaceutical University"},{"subitem_text_value":"Department of Pharmacy, Tottori University Hospital"},{"subitem_text_value":"Division of Clinical Pharmaceutics, Tohoku Medical and Pharmaceutical University"},{"subitem_text_value":"Department of Pharmacy, Tottori University Hospital"},{"subitem_text_value":"Department of Pharmacy, Tottori University Hospital"},{"subitem_text_value":"Laboratory of Environmental and Health Sciences, Tohoku Medical and Pharmaceutical University"},{"subitem_text_language":"en","subitem_text_value":"Department of Pharmacy, Tottori University Hospital"}]},"item_10001_version_type_20":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Ishida,Masako","creatorNameLang":"en"}],"familyNames":[{}],"givenNames":[{}]},{"creatorNames":[{"creatorName":"Kumagai,Takeshi","creatorNameLang":"en"}],"familyNames":[{}],"givenNames":[{}]},{"creatorNames":[{"creatorName":"Yamamoto,Tatsuro","creatorNameLang":"en"}],"familyNames":[{}],"givenNames":[{}]},{"creatorNames":[{"creatorName":"Suzuki,Hiroyuki","creatorNameLang":"en"}],"familyNames":[{}],"givenNames":[{}]},{"creatorNames":[{"creatorName":"Moriki,Kuniaki","creatorNameLang":"en"}],"familyNames":[{}],"givenNames":[{}]},{"creatorNames":[{"creatorName":"Fujiyoshi,Masachika","creatorNameLang":"en"}],"familyNames":[{}],"givenNames":[{}]},{"creatorNames":[{"creatorName":"Nagata,Kiyoshi","creatorNameLang":"en"}],"familyNames":[{}],"givenNames":[{}]},{"creatorAffiliations":[{"affiliationNameIdentifiers":[{}],"affiliationNames":[{},{}]}],"creatorNames":[{"creatorName":"島田,美樹","creatorNameLang":"ja"},{"creatorName":"Shimada,Miki","creatorNameLang":"en"},{"creatorName":"シマダ,ミキエ","creatorNameLang":"ja-Kana"}],"familyNames":[{},{},{}],"givenNames":[{},{},{}],"nameIdentifiers":[{},{},{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2024-02-21"}],"displaytype":"detail","fileDate":[{"fileDateType":"Issued","fileDateValue":"2024-02-21"}],"filename":"yam67(1)_31.pdf","format":"application/pdf","licensefree":"(C)2024 Tottori University Medical Press","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"yam67(1)_31.pdf","objectType":"fulltext","url":"https://repository.lib.tottori-u.ac.jp/record/2001328/files/yam67(1)_31.pdf"},"version_id":"78466b8d-c0d1-4459-b661-04f0bd2b38ee"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"aprepitant","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"CYP3A4","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"drug interaction","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"L-755446","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"voriconazole","subitem_subject_language":"en","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"}]},"item_title":"Mechanism Underlying Conflicting Drug-Drug Interaction Between Aprepitant and Voriconazole via Cytochrome P450 3A4-Mediated Metabolism","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Mechanism Underlying Conflicting Drug-Drug Interaction Between Aprepitant and Voriconazole via Cytochrome P450 3A4-Mediated Metabolism","subitem_title_language":"en"}]},"item_type_id":"10001","owner":"10","path":["12","9","1710471383343"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2024-03-21"},"publish_date":"2024-03-21","publish_status":"0","recid":"2001328","relation_version_is_last":true,"title":["Mechanism Underlying Conflicting Drug-Drug Interaction Between Aprepitant and Voriconazole via Cytochrome P450 3A4-Mediated Metabolism"],"weko_creator_id":"10","weko_shared_id":-1},"updated":"2024-03-15T06:37:46.431798+00:00"}