{"created":"2025-03-11T05:25:59.276477+00:00","id":2015666,"links":{},"metadata":{"_buckets":{"deposit":"bbb1a569-9d4d-4e3c-adf2-ccddef320cb8"},"_deposit":{"created_by":49,"id":"2015666","owner":"49","owners":[49],"pid":{"revision_id":0,"type":"depid","value":"2015666"},"status":"published"},"_oai":{"id":"oai:toho.repo.nii.ac.jp:02015666","sets":["1724837505016:1733473921826:1741652964890"]},"author_link":[],"item_10001_alternative_title_1":{"attribute_name":"その他のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"Cardiac Safety Evaluation of New Drug Candidates Based on the Latest ICH E14/S7B Q&A","subitem_alternative_title_language":"en"}]},"item_10001_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2025-03-01","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"1","bibliographicPageEnd":"36","bibliographicPageStart":"31","bibliographicVolumeNumber":"72","bibliographic_titles":[{"bibliographic_title":"東邦医学会雑誌","bibliographic_titleLang":"ja"},{"bibliographic_title":"Journal of the Medical Society of Toho University","bibliographic_titleLang":"en"}]}]},"item_10001_description_6":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"最終講義","subitem_description_language":"ja","subitem_description_type":"Other"},{"subitem_description":"2005年に薬物性QT延長症候群の発生を回避するために制定されたICH S7B/E14ガイドラインは，催不整脈リスクが証明されていない潜在的に価値ある化合物の開発を阻害するものであった．2013年にCSRC/HESI/FDA主導のシンクタンク会議は新規候補化合物の催不整脈作用のリスク評価を推進するために，「包括的in vitro催不整脈評価」と「曝露-反応モデリング」を提案した．2022年にはICHは「ダブルネガティブ」化合物の臨床試験における安全性評価の進め方を記載した最新E14/S7B Q＆A（Stage 1）を採択した．また，「非ダブルネガティブ」化合物に対する新たなQ＆A（Stage 2）の策定も進行中である．本総説では，これらQ＆Aの適切な運用に必要となる薬物性トルサード・ド・ポアントの発生メカニズムおよび代替指標を用いた致死性不整脈の発生予測法について掘り下げ，抗がん薬などの心臓安全性評価への展開を紹介した．これらの洞察は，新薬候補化合物の心臓安全性評価にこの新しいQ＆Aを効果的に応用するために極めて重要である．The ICH S7B/E14 guidelines, established in 2005, aimed to prevent drug-induced long QT syndrome but inadvertently hindered the development of potentially beneficial compounds lacking demonstrated proarrhythmic risk. In response, a CSRC/HESI/FDA-led think tank in 2013 introduced concepts comprising “comprehensive in vitro proarrhythmia assay” and “exposure-response modeling” to enhance the risk assessment of new drug candidates' proarrhythmic effects. By 2022, the ICH formally adopted an updated E14/S7B Q&A (Stage 1) outlining procedures for the safety assessment of double negative compounds in clinical trials. Moreover, a new Q&A (Stage 2) addressing non-double negative compounds is currently under development. This review explores the mechanisms underlying drug-induced torsade de pointes using surrogate markers to predict lethal arrhythmias. These insights are crucial for the effective application of the new Q&A in assessing the cardiac safety of new drug candidates.","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_10001_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.14994/tohoigaku.2024-061","subitem_identifier_reg_type":"JaLC"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"東邦大学医学会","subitem_publisher_language":"ja"},{"subitem_publisher":"トウホウダイガク イガクカイ","subitem_publisher_language":"ja-Kana"},{"subitem_publisher":"The Medical Society of Toho University","subitem_publisher_language":"en"}]},"item_10001_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"00408670","subitem_source_identifier_type":"PISSN"}]},"item_10001_version_type_20":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_1726887212651":{"attribute_name":"資源タイプ(ローカル)","attribute_value_mlt":[{"subitem_description":"TOHO University Scholarly Publication","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorAffiliations":[{"affiliationNames":[{"affiliationName":"東邦大学医学部薬理学講座","affiliationNameLang":"ja"}]}],"creatorNames":[{"creatorName":"杉山, 篤","creatorNameLang":"ja"},{"creatorName":"スギヤマ, アツシ","creatorNameLang":"ja-Kana"},{"creatorName":"SUGIYAMA, ATSUSHI","creatorNameLang":"en"}],"creatorType":"Author"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","displaytype":"detail","filename":"2015666.pdf","filesize":[{"value":"572.2 KB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"url":"https://toho.repo.nii.ac.jp/record/2015666/files/2015666.pdf"},"version_id":"76be05e8-805b-4065-8f06-1aa743cb41e3"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"医薬品規制調和国際会議E14/S7B Q&A","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"薬物性QT延長症候群","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"再分極予備力","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"トルサード・ド・ポアント","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"ICH E14/S7B Q&A","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"drug-induced long QT syndrome","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"repolarization reserve","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"torsade de pointes","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":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"最新ICH E14/S7B Q＆Aに基づく新薬候補化合物の心臓安全性評価","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"最新ICH E14/S7B Q＆Aに基づく新薬候補化合物の心臓安全性評価","subitem_title_language":"ja"},{"subitem_title":"サイシン ICHE14/S7B Q&A ニ モトヅク シンヤク コウホ カゴウブツ ノ シンゾウ アンゼンセイ ヒョウカ","subitem_title_language":"ja-Kana"}]},"item_type_id":"10001","owner":"49","path":["1741652964890"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2025-03-11"},"publish_date":"2025-03-11","publish_status":"0","recid":"2015666","relation_version_is_last":true,"title":["最新ICH E14/S7B Q＆Aに基づく新薬候補化合物の心臓安全性評価"],"weko_creator_id":"49","weko_shared_id":-1},"updated":"2025-03-11T07:20:57.237739+00:00"}