{"created":"2023-06-20T15:49:13.113087+00:00","id":3792,"links":{},"metadata":{"_buckets":{"deposit":"569f91ca-47f5-4864-b8e1-e07113b558a1"},"_deposit":{"created_by":4,"id":"3792","owners":[4],"pid":{"revision_id":0,"type":"depid","value":"3792"},"status":"published"},"_oai":{"id":"oai:hama-med.repo.nii.ac.jp:00003792","sets":["1:11"]},"author_link":[],"item_3_alternative_title_1":{"attribute_name":"その他のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"Effect of clopidogrel on selexipag PK"}]},"item_3_biblio_info_5":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2021-04","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"4","bibliographicPageEnd":"1911","bibliographicPageStart":"1903","bibliographicVolumeNumber":"87","bibliographic_titles":[{"bibliographic_title":"British Journal of Clinical Pharmacology"}]}]},"item_3_description_9":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Aims: The strong cytochrome P450 (CYP) 2C8 inhibitor gemfibrozil has been demonstrated to increase the area under the plasma concentration-time curve from 0 to infinity (AUC0?∞) of ACT-333679, an active metabolite of selexipag, by 11-fold. Similarly as gemfibrozil, the CYP2C8 inhibitor clopidogrel also increases clopidogrel increased ACT-333679 concentration by 1.9-fold after a single loading dose (300 mg once daily) and 2.7-fold after repeated treatment with the maintenance dose (75 mg once daily) in Europeans. However, the effects of clopidogrel on the pharmacokinetics of selexipag and ACT-333679 have not been fully elucidated in Japanese population.\nMethods: We investigated the effect of clopidogrel on the pharmacokinetics of selexipag and ACT-333679 in 14 healthy Japanese volunteers.\nResults: The concomitant administration of clopidogrel with selexipag did not influence the maximum concentration (Cmax) and AUC0-∞ of selexipag, whereas it significantly increased AUC0-∞ of ACT-333679 by approximately 1.90-fold (90% confidence interval (CI) 1.69?2.14) without changing Cmax. When selexipag was administered 1 day after clopidogrel was discontinued, the increase in AUC0-∞ of ACT-333679 was 1.37-fold (90% CI 0.93?2.02), suggesting that although the inhibitory effect of clopidogrel on CYP2C8 was reduced, it persisted for at least 1 day after withdrawal.\nConclusion: Our results demonstrated the impact of clopidogrel on the pharmacokinetics of selexipag and its active metabolite and suggested that selexipag should be carefully prescribed with clopidogrel with dose adjustment or reducing the dosing frequency in Japanese clinical settings.","subitem_description_type":"Abstract"}]},"item_3_publisher_6":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"John Wiley and Sons "}]},"item_3_relation_26":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"32997809","subitem_relation_type_select":"PMID"}}]},"item_3_relation_28":{"attribute_name":"出版社DOI","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1111/bcp.14579","subitem_relation_type_select":"DOI"}}]},"item_3_rights_7":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"\"This is the peer reviewed version of the following article: \"\"Clinical evaluation of drug?drug interactions between the cytochrome P450 substrates selexipag and clopidogrel in Japanese volunteers\"\", British Journal of Clinical Pharmacology; 87(4): p1903-1911, 2021, which has been published in final form at https://doi.org/10.1111/bcp.14579. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.\""}]},"item_3_source_id_19":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0306-5251","subitem_source_identifier_type":"ISSN"}]},"item_3_source_id_20":{"attribute_name":"EISSN","attribute_value_mlt":[{"subitem_source_identifier":"1365-2125","subitem_source_identifier_type":"ISSN"}]},"item_3_version_type_32":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Katayama, Naoki"}]},{"creatorNames":[{"creatorName":"Odagiri, Keiichi"}]},{"creatorNames":[{"creatorName":"Hakamata, Akio"}]},{"creatorNames":[{"creatorName":"Kamiya, Chiaki"}]},{"creatorNames":[{"creatorName":"Uchida, Shinya"}]},{"creatorNames":[{"creatorName":"Tanaka, Shimako"}]},{"creatorNames":[{"creatorName":"Inui, Naoki"}]},{"creatorNames":[{"creatorName":"Namiki, Noriyuki"}]},{"creatorNames":[{"creatorName":"Tatsumi, Koichiro"}]},{"creatorNames":[{"creatorName":"Watanabe, Hiroshi"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-11-16"}],"displaytype":"detail","filename":"BJCP-87-1903.pdf","filesize":[{"value":"945.7 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"BJCP-87-1903.pdf","url":"https://hama-med.repo.nii.ac.jp/record/3792/files/BJCP-87-1903.pdf"},"version_id":"6b7a67cf-7ae4-4185-8d42-944d9fd85420"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"CYP","subitem_subject_scheme":"Other"},{"subitem_subject":"drug-drug interaction","subitem_subject_scheme":"Other"},{"subitem_subject":"pharmacokinetics","subitem_subject_scheme":"Other"},{"subitem_subject":"clopidogrel","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":"Clinical evaluation of drug?drug interactions between the cytochrome P450 substrates selexipag and clopidogrel in Japanese volunteers","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Clinical evaluation of drug?drug interactions between the cytochrome P450 substrates selexipag and clopidogrel in Japanese volunteers","subitem_title_language":"en"}]},"item_type_id":"3","owner":"4","path":["11"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2021-11-01"},"publish_date":"2021-11-01","publish_status":"0","recid":"3792","relation_version_is_last":true,"title":["Clinical evaluation of drug?drug interactions between the cytochrome P450 substrates selexipag and clopidogrel in Japanese volunteers"],"weko_creator_id":"4","weko_shared_id":-1},"updated":"2023-08-02T07:42:43.925980+00:00"}