{"@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/1390001205657544576.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.14869/toxp.36.0.4100.0"}},{"identifier":{"@type":"NAID","@value":"130007002861"}}],"dc:title":[{"@language":"en","@value":"application of a probabilistic analysis for the determination of QT prolongation in telemetered dogs"},{"@language":"ja","@value":"テレメトリーイヌにおけるprobabilistic解析によるQT延長作用の高精度評価"}],"dc:language":"ja","description":[{"type":"abstract","notation":[{"@language":"ja","@value":"【目的】QT間隔はRR間隔の変動に伴って変化するが,同一RR間隔においてもQT間隔は大きく分散することが知られている。これはQT間隔の補正を不正確にする原因の一つとして挙げられ，より精度の高い解析法が望まれている。2007年，この問題点をクリアした新規QT間隔解析法（probabilistic解析）が，サル・イヌを用いた検討で報告された（Holzgrefe et al., 2007）。そこで我々は，心電図電極を心外膜に装着したテレメトリーイヌの臨床予測性について検討するためThorough QT/QTc試験における陽性対照薬（moxifloxacin）によるQT延長作用をprobabilistic解析法により検討し、その検出感度を確認した。\n【方法】テレメトリー送信器の心電図電極を心外膜に縫合したビーグル犬（CMS; 雌雄各3匹）を使用し，無麻酔・無拘束下にて心電図，心拍数及び血圧を測定した。取得した全波形からRR間隔10ミリ秒ごとのQT間隔の平均値を算出し，個別補正式（Miyazaki et al., 2002）を求めた。Moxifloxacin（0，3，10，30 mg/kg）はラテン方格法に従って単回経口投与し，5分間ごとに補正QT間隔（QTc）の平均値を求め，QT延長作用を評価した。\n【結果及び考察】Probabilistic解析法から得られた個別補正式を用いて算出されたQTcは，RR間隔変動に対して非常に安定していた（slope = 0.00017±0.00070，CV = 0.94±0.19％）。Moxifloxacinの検討では，10 mg/kgの投与からQTcの延長が認められ，その他の心循環パラメータに変化は認められなかった。以上のことから，probabilistic解析法を用いたイヌのテレメトリー試験系が臨床におけるQT延長作用を予測する上で有用な非臨床評価系であることが明らかとなった。"}],"abstractLicenseFlag":"disallow"}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1410853646188105728","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000391993018"}],"foaf:name":[{"@language":"en","@value":"ISOBE TAKEHITO"},{"@language":"ja","@value":"礒部 剛仁"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Chugai Pharmaceutical CO., LTD. Fuji Gotemba Research Laboratories. Safety Assessment Department"},{"@language":"ja","@value":"中外製薬株式会社　富士御殿場研究所　安全性研究部"}]},{"@id":"https://cir.nii.ac.jp/crid/1410853646188105731","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000391993019"}],"foaf:name":[{"@language":"en","@value":"KOMATSU RYUICHI"},{"@language":"ja","@value":"小松 竜一"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Chugai Pharmaceutical CO., LTD. Fuji Gotemba Research Laboratories. Safety Assessment Department"},{"@language":"ja","@value":"中外製薬株式会社　富士御殿場研究所　安全性研究部"}]},{"@id":"https://cir.nii.ac.jp/crid/1410001204900788352","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000006858671"}],"foaf:name":[{"@language":"en","@value":"HONDA MASAKI"},{"@language":"ja","@value":"本多 正樹"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Chugai Pharmaceutical CO., LTD. Fuji Gotemba Research Laboratories. Safety Assessment Department"},{"@language":"ja","@value":"中外製薬株式会社　富士御殿場研究所　安全性研究部"}]},{"@id":"https://cir.nii.ac.jp/crid/1410853646188105729","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000391993021"}],"foaf:name":[{"@language":"en","@value":"YAMADA YUICHIRO"},{"@language":"ja","@value":"山田 裕一郎"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Chugai Pharmaceutical CO., LTD. Fuji Gotemba Research Laboratories. Safety Assessment Department"},{"@language":"ja","@value":"中外製薬株式会社　富士御殿場研究所　安全性研究部"}]},{"@id":"https://cir.nii.ac.jp/crid/1410853646188105733","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000391993022"}],"foaf:name":[{"@language":"en","@value":"KIMURA KAZUYA"},{"@language":"ja","@value":"木村 和哉"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Chugai Pharmaceutical CO., LTD. Fuji Gotemba Research Laboratories. Safety Assessment Department"},{"@language":"ja","@value":"中外製薬株式会社　富士御殿場研究所　安全性研究部"}]},{"@id":"https://cir.nii.ac.jp/crid/1410853646188105730","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000391993023"}],"foaf:name":[{"@language":"en","@value":"TABO MITSUYASU"},{"@language":"ja","@value":"田保 充康"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Chugai Pharmaceutical CO., LTD. Fuji Gotemba Research Laboratories. Safety Assessment Department"},{"@language":"ja","@value":"中外製薬株式会社　富士御殿場研究所　安全性研究部"}]}],"publication":{"prism:publicationName":[{"@language":"en","@value":"Annual Meeting of the Japanese Society of Toxicology"},{"@language":"ja","@value":"日本トキシコロジー学会学術年会"},{"@language":"en","@value":"Annual Meeting of the Japanese Society of Toxicology"},{"@language":"ja","@value":"日本トキシコロジー学会学術年会"}],"dc:publisher":[{"@language":"en","@value":"The Japanese Society of Toxicology"},{"@language":"ja","@value":"日本毒性学会"}],"prism:publicationDate":"2009","prism:volume":"36","prism:number":"0","prism:startingPage":"4100","prism:endingPage":"4100"},"availableAt":"2009","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=%E3%83%86%E3%83%AC%E3%83%A1%E3%83%88%E3%83%AA%E3%83%BC%E3%82%A4%E3%83%8C","dc:title":"テレメトリーイヌ"},{"@id":"https://cir.nii.ac.jp/all?q=probailistic","dc:title":"probailistic"},{"@id":"https://cir.nii.ac.jp/all?q=%E5%BF%83%E9%9B%BB%E5%9B%B3","dc:title":"心電図"},{"@id":"https://cir.nii.ac.jp/all?q=telemetered%20dogs","dc:title":"telemetered dogs"},{"@id":"https://cir.nii.ac.jp/all?q=probailistic","dc:title":"probailistic"},{"@id":"https://cir.nii.ac.jp/all?q=electrocardiogram","dc:title":"electrocardiogram"}],"dataSourceIdentifier":[{"@type":"JALC","@value":"oai:japanlinkcenter.org:1003279865"},{"@type":"CIA","@value":"130007002861"}]}