{"created":"2025-01-22T06:12:26.149999+00:00","id":2000288,"links":{},"metadata":{"_buckets":{"deposit":"794ca32d-c9f0-4a62-861e-6dd6b74a1b61"},"_deposit":{"created_by":3,"id":"2000288","owner":"3","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"2000288"},"status":"published"},"_oai":{"id":"oai:asahikawa-med.repo.nii.ac.jp:02000288","sets":["7:27:45"]},"author_link":[],"item_10_alternative_title_3":{"attribute_name":"その他（別言語等）のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"エンタカポン併用下におけるL-dopaおよびその代謝物である3-O-メチルドパの体内動態に及ぼすカテコール-O-メチルトランスフェラーゼVal158Met遺伝子多型の影響に関する研究","subitem_alternative_title_language":"ja"}]},"item_10_biblio_info_21":{"attribute_name":"bibliographic_information","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2021-01-01","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"1","bibliographicPageEnd":"36","bibliographicPageStart":"27","bibliographicVolumeNumber":"128","bibliographic_titles":[{"bibliographic_title":"Journal of Neural Transmission","bibliographic_titleLang":"en"}]}]},"item_10_date_granted_30":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2021-09-30"}]},"item_10_degree_grantor_32":{"attribute_name":"item_10_degree_grantor_32","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"旭川医科大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"10107","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_10_degree_name_31":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）","subitem_degreename_language":"ja"}]},"item_10_description_28":{"attribute_name":"識別番号 その他","attribute_value_mlt":[{"subitem_description":"PMID:33136226","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_10_description_33":{"attribute_name":"item_10_description_33","attribute_value_mlt":[{"subitem_description":"In the pharmacotherapy of patients with Parkinson's disease (PD), entacapone reduces the peripheral metabolism of L-dopa to 3-O-methyldopa (3-OMD), thereby prolonging the half-life (t1/2) of L-dopa and increasing the area under the concentration curve (AUC). The effect of entacapone on the pharmacokinetics of L-dopa differs between patients with high-activity (H/H) and low-activity (L/L) catechol-O-methyltransferase (COMT) Val158Met polymorphisms, but the effects are unclear in heterozygous (H/L) patients. 3-OMD has a detrimental effect and results in a poor response to L-dopa treatment in patients with PD; however, the influence of this polymorphism on the production of 3-OMD remains unknown. Therefore, the present study aimed to clarify the effect of the COMT Val158Met polymorphism on the concentrations of L-dopa and 3-OMD in the presence of entacapone. We performed an open-label, single-period, single-sequence crossover study at two sites in Japan. The study included 54 Japanese patients with PD, who underwent an acute L-dopa administration test with and without 100 mg entacapone on two different days. Entacapone increased L-dopa AUC0-infinity by 1.59 ± 0.26-fold in the H/H group, which was significantly higher than that in the H/L (1.41 ± 0.36-fold) and L/L (1.28 ± 0.21-fold) groups (p < 0.05). The concurrent administration of L-dopa with entacapone suppressed the increase in 3-OMD levels compared with L-dopa alone in all genotypes. Our results suggest that the COMT Val158Met polymorphism may be an informative biomarker for individualized dose adjustment of COMT inhibitors in the treatment of PD.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10_dissertation_number_29":{"attribute_name":"dissertation_number","attribute_value_mlt":[{"subitem_dissertationnumber":"乙第490号"}]},"item_10_relation_24":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1007/s00702-020-02267-y","subitem_relation_type_select":"DOI"}}]},"item_10_version_type_38":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"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":"山本, 譲","creatorNameLang":"ja","creatorNameType":"Personal"},{"creatorName":"ヤマモト, ジョウ","creatorNameLang":"ja-Kana","creatorNameType":"Personal"},{"creatorName":"Yamamoto, Joe","creatorNameLang":"en","creatorNameType":"Personal"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2022-07-05"}],"filename":"O490 Yamamoto Joe_TD.pdf","filesize":[{"value":"521 KB"}],"format":"application/pdf","url":{"objectType":"fulltext","url":"https://asahikawa-med.repo.nii.ac.jp/record/2000288/files/O490 Yamamoto Joe_TD.pdf"},"version_id":"b4edc615-4fe9-41ca-b278-bb7665b0c137"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"3-O-Methyldopa","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Catechol-O-methyl transferase","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Entacapone","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"L-dopa","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Parkinson’s disease","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Polymorphism","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":"item_resource_type","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Impact of the Catechol-O-Methyltransferase Val158Met Polymorphism on the Pharmacokinetics of L-dopa and its Metabolite 3-O-Methyldopa in Combination with Entacapone","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Impact of the Catechol-O-Methyltransferase Val158Met Polymorphism on the Pharmacokinetics of L-dopa and its Metabolite 3-O-Methyldopa in Combination with Entacapone","subitem_title_language":"en"}]},"item_type_id":"10","owner":"3","path":["45"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2022-07-05"},"publish_date":"2022-07-05","publish_status":"0","recid":"2000288","relation_version_is_last":true,"title":["Impact of the Catechol-O-Methyltransferase Val158Met Polymorphism on the Pharmacokinetics of L-dopa and its Metabolite 3-O-Methyldopa in Combination with Entacapone"],"weko_creator_id":"3","weko_shared_id":-1},"updated":"2025-01-22T06:17:30.067554+00:00"}