{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1390282679645167232.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.2133/dmpk.13.546"}},{"identifier":{"@type":"URI","@value":"http://www.jstage.jst.go.jp/article/dmpk1986/13/6/13_6_546/_pdf"}},{"identifier":{"@type":"NAID","@value":"10008199030"}},{"identifier":{"@type":"URI","@value":"https://search.jamas.or.jp/link/ui/1999110775"}}],"dc:title":[{"@language":"en","@value":"Studies on the Metabolic Fate of a Novel Orally Active Nonpeptide Endothelin Antagonist TA-0201: Metabolism and First-pass Metabolism of TA-0201 in Rats."},{"@value":"新規エンドセリン受容体きっ抗薬（ＴＡ‐０２０１）の体内動態　ラットにおける代謝と初回通過効果"}],"dc:language":"ja","description":[{"type":"abstract","notation":[{"@language":"en","@value":"TA-0201 is a novel orally active non-peptide antagonist for endothelin receptors. Metabolism and pharmacokinetics of TA-0201 were investigated in rat. Animal and human liver microsomes were used to investigate the metabolism of TA-0201 <I>in vitro</I>.<BR> 1. The structures of main metabolites were identified to be carboxylic acid form (CA) and diol form (Diol) by comparison with authentic sample using LC/MS/MS. Intrinsic clearances (CLint) for the conversion of TA-0201 to CA by liver microsomes of different species were in the following order of monkey>>dog>human>rat. The isozyme catalyzing the metabolic reaction of TA-0201 to CA and Diol was determined. It was supposed that CYP3A family contributed mainly to these metabolic reactions.<BR> 2. Pharmacokinetic studies of TA-0201 in the rat were investigated, the bioavailability (BA) in male rats was calculated as 60%. More than 90% of TA-0201 was disappeared from the body by metabolism. Hepatic and gastro intestinal extractions were 0.21 and 0.11, respectively. Contributions of the two organs in the first-pass extraction of TA-0201 after oral administration were of the same degree."},{"@value":"TA-0201は非ペプチド性の新規エソドセリン受容体拮抗薬である．TA-0201のラットにおける代謝および体内動態について検討した．さらに，ヒトを含めた各動物種肝ミクロゾームを用いて<I>in vitro</I>における代謝について検討した．<BR> 1．TA-0201の主代謝はカルボソ酸体(CA)およびジオール体(Diol)への酸化反応であり，各動物種の肝ミクロゾームにおけるTA-0201からCAへの代謝固有クリアランス(<I>in vitro</I>)はサル>>イヌ>ヒト>ラットの順で大きいことが判明した．また，TA-0201からCAおよびジオール体への代謝反応にはCYP3A Familyが主に関与していることが推定された．<BR> 2．TA-0201のラットにおける血漿中動態を薬物速度論的に解析したところ，経口および静脈内投与時の血漿中濃度推移から求めたBAは約60%と良好であり，本化合物はラットの体内からほぼ90%以上が代謝により消失し，その代謝臓器は主に肝臓と消化管であることが示唆された．肝および消化管における臓器抽出率はそれぞれ0.21および0.11であり，両臓器における初回通過効果の寄与はほぼ同程度であると推定された．"}],"abstractLicenseFlag":"disallow"}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1410001204669387906","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000000713830"},{"@type":"NRID","@value":"9000020423002"}],"foaf:name":[{"@language":"en","@value":"OHASHI Noriko"},{"@language":"ja","@value":"大橋 徳子"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Pharmaceutical Development Research Laboratory, Tanabe Seiyaku Co., Ltd"},{"@language":"ja","@value":"田辺製薬株式会社医薬開発研究所"}]},{"@id":"https://cir.nii.ac.jp/crid/1410001204670189701","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000000637734"}],"foaf:name":[{"@language":"en","@value":"OHASHI Rikiya"},{"@language":"ja","@value":"大橋 力也"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Pharmaceutical Development Research Laboratory, Tanabe Seiyaku Co., Ltd"},{"@language":"ja","@value":"田辺製薬株式会社医薬開発研究所"}]},{"@id":"https://cir.nii.ac.jp/crid/1410001204669387904","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000005200723"},{"@type":"NRID","@value":"9000252831419"},{"@type":"NRID","@value":"9000415146378"}],"foaf:name":[{"@language":"en","@value":"YOSHIKAWA Masayoshi"},{"@language":"ja","@value":"吉川 正美"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Pharmaceutical Development Research Laboratory, Tanabe Seiyaku Co., Ltd"},{"@language":"ja","@value":"田辺製薬株式会社医薬開発研究所"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"09161139"},{"@type":"NCID","@value":"AN10144117"}],"prism:publicationName":[{"@language":"en","@value":"Drug Metabolism and Pharmacokinetics"},{"@language":"ja","@value":"薬物動態"},{"@language":"en","@value":"Drug Metabolism and Pharmacokinetics"},{"@language":"ja","@value":"薬物動態"}],"dc:publisher":[{"@language":"en","@value":"The Japanese Society for the Study of Xenobiotics"},{"@language":"ja","@value":"日本薬物動態学会"}],"prism:publicationDate":"1998","prism:volume":"13","prism:number":"6","prism:startingPage":"546","prism:endingPage":"556"},"reviewed":"false","url":[{"@id":"http://www.jstage.jst.go.jp/article/dmpk1986/13/6/13_6_546/_pdf"},{"@id":"https://search.jamas.or.jp/link/ui/1999110775"}],"availableAt":"1998","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=TA-0201","dc:title":"TA-0201"},{"@id":"https://cir.nii.ac.jp/all?q=LC/MS/MS","dc:title":"LC/MS/MS"},{"@id":"https://cir.nii.ac.jp/all?q=Metabolism","dc:title":"Metabolism"},{"@id":"https://cir.nii.ac.jp/all?q=Species%20difference","dc:title":"Species difference"},{"@id":"https://cir.nii.ac.jp/all?q=Pharmacokinetics","dc:title":"Pharmacokinetics"},{"@id":"https://cir.nii.ac.jp/all?q=Rat","dc:title":"Rat"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360290617673125248","@type":"Article","resourceType":"学術雑誌論文(journal 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antagonist"}]},{"@id":"https://cir.nii.ac.jp/crid/1571135649652501888","@type":"Article","relationType":["cites"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Pharmacological profile of TA-0201, a potent nonpeptide endothelin antagonist, and preferable effects in models of pulmonary hypertension induced by monocrotaline"}]},{"@id":"https://cir.nii.ac.jp/crid/1571980074582633856","@type":"Article","relationType":["cites"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Drug metabolism in human liver in vitro: Establishment of a human liver bank"}]},{"@id":"https://cir.nii.ac.jp/crid/1572261549559344512","@type":"Article","relationType":["cites"]},{"@id":"https://cir.nii.ac.jp/crid/1572824501565401984","@type":"Article","relationType":["cites"]},{"@id":"https://cir.nii.ac.jp/crid/1573105974487160448","@type":"Article","relationType":["cites"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Identification of glucocorticoid-inducible cytochromes P-450 in the intestinal mucosa 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