{"_buckets": {"deposit": "f53051e0-7fb5-402c-8a96-fb7f80f36fb0"}, "_deposit": {"created_by": 4, "id": "12939", "owners": [4], "pid": {"revision_id": 0, "type": "depid", "value": "12939"}, "status": "published"}, "_oai": {"id": "oai:gifu-pu.repo.nii.ac.jp:00012939", "sets": ["217"]}, "author_link": ["17999", "17998", "17997"], "item_1_biblio_info_14": {"attribute_name": "書誌情報", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2011-06-30", "bibliographicIssueDateType": "Issued"}, "bibliographicPageEnd": "32", "bibliographicPageStart": "23", "bibliographicVolumeNumber": "60", "bibliographic_titles": [{"bibliographic_title": "岐阜薬科大学紀要"}, {"bibliographic_title": "The annual proceedings of Gifu Pharmaceutical University", "bibliographic_titleLang": "en"}]}]}, "item_1_creator_6": {"attribute_name": "著者名(日)", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "小笠原, 明人"}], "nameIdentifiers": [{"nameIdentifier": "17997", "nameIdentifierScheme": "WEKO"}]}]}, "item_1_creator_7": {"attribute_name": "著者名よみ", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "オガサワラ, アキヒト"}], "nameIdentifiers": [{"nameIdentifier": "17998", "nameIdentifierScheme": "WEKO"}]}]}, "item_1_creator_8": {"attribute_name": "著者名(英)", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "OGASAWARA, Akihito", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "17999", "nameIdentifierScheme": "WEKO"}]}]}, "item_1_description_1": {"attribute_name": "ページ属性", "attribute_value_mlt": [{"subitem_description": "P(論文)", "subitem_description_type": "Other"}]}, "item_1_description_11": {"attribute_name": "抄録(日)", "attribute_value_mlt": [{"subitem_description": "医薬品開発過程で開発候補化合物の薬物相互作用の可能性を見極めることは、安全な医薬品を開発する上で重要である。本総説では、著者らの研究に基づき、カニクイサルを用いて主要な薬物代謝酵素であるシトクロムP450（CYP）3Aが関与する薬物相互作用試験のヒトへの外挿性について述べる。カニクイサルにCYP3Aのプローブ薬物であるミダゾラム（1 mg/kg）またはシンバスタチン（20 mg/kg）を経口投与した時、両薬物の血漿中濃度は可逆的なCYP3A阻害剤であるケトコナゾールを併用投与（経口投与：5 mg/kg、20 mg/kg）することによって著しく上昇した。また、カニクイサルにおける血漿中ミダゾラム濃度は、ヒトCYP3Aに対する不可逆的な阻害剤であるマクロライド系抗生物質（エリスロマイシン、クラリスロマイシン、アジスロマイシン）を反復経口投与（15 mg/kg，1日2回，3日間）することによって顕著に上昇した。さらに、エリスロマイシンおよびクラリスロマイシンに関しては、反復経口投与が終了した翌日もミダゾラムの血漿中動態に及ぼす作用が持続した。以上、カニクイサルで認められたCYP3A阻害に起因する薬物相互作用は、いずれもヒトにおいて報告されている結果と同程度であることが明らかになった。したがって、カニクイサルを用いた本試験系は、開発候補化合物の臨床における薬物相互作用の危険性を評価するために有用であると考えられた。", "subitem_description_type": "Other"}]}, "item_1_description_12": {"attribute_name": "抄録(英)", "attribute_value_mlt": [{"subitem_description": "It is important to assess the potential for drug candidates to cause drug-drug interactions (DDIs) during drug development. This review describes the usefulness, based on our recent studies, of an animal model using cynomolgus monkeys for the prediction of clinical DDIs caused by inhibition of cytochrome P450 (CYP) 3A, a major drug-metabolizing enzyme in humans. Following oral dosing of midazolam (1 mg/kg) or simvastatin (20 mg/kg), typical substrates for CYP3A, to cynomolgus monkeys, the plasma concentrations of the two drugs were significantly increased by coadministration of ketoconazole (oral: 5 mg/kg, 20 mg/kg), a typical reversible inhibitor of human CYP3A. Furthermore, midazolam concentrations in plasma were significantly increased after repeated oral dosing of macrolide antibiotics, erythromycin, clarithromycin or azithromycin, which are irreversible inhibitors of human CYP3A. In addition, the effects of erythromycin and clarithromycin on the pharmacokinetics of midazolam were maintained on the day after completion of treatment of the macrolide antibiotics. Thus, the results of the DDIs studies using cynomolgus monkeys were similar to those in humans, suggesting that the cynomolgus monkey is a suitable animal model for the prediction of clinical DDIs caused by CYP3A inhibition.", "subitem_description_type": "Other"}]}, "item_1_source_id_13": {"attribute_name": "雑誌書誌ID", "attribute_value_mlt": [{"subitem_source_identifier": "AA1258935X", "subitem_source_identifier_type": "NCID"}]}, "item_1_text_10": {"attribute_name": "著者所属(英)", "attribute_value_mlt": [{"subitem_text_language": "en", "subitem_text_value": "DMPK Research Laboratories, Mitsubishi Tanabe Pharma Corporation"}]}, "item_1_text_2": {"attribute_name": "記事種別(日)", "attribute_value_mlt": [{"subitem_text_value": "総説"}]}, "item_1_text_3": {"attribute_name": "記事種別(英)", "attribute_value_mlt": [{"subitem_text_language": "en", "subitem_text_value": "Review"}]}, "item_1_text_9": {"attribute_name": "著者所属(日)", "attribute_value_mlt": [{"subitem_text_value": "田辺三菱株式会社 薬物動態研究所"}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2014-07-29"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "カニクイサルを用いた薬物相互作用試験のヒトへの外挿性に関する研究.pdf", "filesize": [{"value": "667.5 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_11", "mimetype": "application/pdf", "size": 667500.0, "url": {"label": "カニクイサルを用いた薬物相互作用試験のヒトへの外挿性に関する研究", "url": "https://gifu-pu.repo.nii.ac.jp/record/12939/files/カニクイサルを用いた薬物相互作用試験のヒトへの外挿性に関する研究.pdf"}, "version_id": "dc3a5d8b-cb9b-491d-aaaf-c9924dc9cce4"}]}, "item_keyword": {"attribute_name": "キーワード", "attribute_value_mlt": [{"subitem_subject": "薬物相互作用", "subitem_subject_scheme": "Other"}, {"subitem_subject": "カニクイサル", "subitem_subject_scheme": "Other"}, {"subitem_subject": "シトクロムP450", "subitem_subject_scheme": "Other"}, {"subitem_subject": "アゾール系抗真菌薬", "subitem_subject_scheme": "Other"}, {"subitem_subject": "マクロライド系抗生物質", "subitem_subject_scheme": "Other"}, {"subitem_subject": "mechanism-based inhibitor", "subitem_subject_scheme": "Other"}, {"subitem_subject": "ミダゾラム", "subitem_subject_scheme": "Other"}, {"subitem_subject": "シンバスタチン", "subitem_subject_scheme": "Other"}, {"subitem_subject": "drug-drug interaction", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}, {"subitem_subject": "cynomolgus monkey", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}, {"subitem_subject": "cytochrome P450", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}, {"subitem_subject": "azole antifungal", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}, {"subitem_subject": "macrolid antibiotic", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}, {"subitem_subject": "mechanism-based inhibitor", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}, {"subitem_subject": "midazolam", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}, {"subitem_subject": "simvastatin", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "jpn"}]}, "item_resource_type": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "departmental bulletin paper", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "カニクイサルを用いた薬物相互作用試験のヒトへの外挿性に関する研究", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "カニクイサルを用いた薬物相互作用試験のヒトへの外挿性に関する研究"}, {"subitem_title": "Usefulness of an Animal Model Using Cynomolgus Monkeys for Prediction of Drug-drug Interaction in Humans", "subitem_title_language": "en"}]}, "item_type_id": "1", "owner": "4", "path": ["217"], "permalink_uri": "https://gifu-pu.repo.nii.ac.jp/records/12939", "pubdate": {"attribute_name": "公開日", "attribute_value": "2014-07-29"}, "publish_date": "2014-07-29", "publish_status": "0", "recid": "12939", "relation": {}, "relation_version_is_last": true, "title": ["カニクイサルを用いた薬物相互作用試験のヒトへの外挿性に関する研究"], "weko_shared_id": -1}