{"@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/1390282680522927488.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.14869/toxpt.40.1.0.1023.0"}},{"identifier":{"@type":"NAID","@value":"130004676557"}}],"dc:title":[{"@language":"en","@value":"Evaluation of drug interactions in the efflux process mediated by drug transporters"},{"@language":"ja","@value":"薬物トランスポーターによる細胞内からの排出輸送過程における薬物相互作用の評価"}],"dc:language":"ja","description":[{"type":"abstract","notation":[{"@language":"ja","@value":"トランスポーターは薬物の消化管吸収、肝・腎排泄、血液脳関門における能動的関門機構として機能している。市販の医薬品の中には、トランスポーター機能を阻害するものがあり、薬物間相互作用として被相互作用薬の体内動態に影響を与え、その結果、薬効・副作用発現に影響を与える。肝胆系輸送や腎尿細管分泌において、組織内への取り込みおよび胆汁・尿中への排出の両輸送過程にトランスポーターが関連する場合、取り込み過程の相互作用は血漿中濃度の強く影響を与えるのに対して、排出過程における相互作用が血液中に与える影響は、薬物の律速段階に依存する。取り込み律速となる場合、血中に与える影響は小さいものの、組織中濃度は排出輸送の低下に応じて増加する。カチオン性薬物ｎ腎尿細管分泌において、こうした事例を見いだした。Pyrimethamineやcimetidineは、H<sup>+</sup>/有機カチオン交換輸送体（MATE）を阻害するが、基底膜側トランスポーターに対する阻害定数は大きく、<I>in vivo</I>での相互作用は小さいことが期待される。実際、マウスでは、これら薬物の投与により、腎組織中濃度の増加が観察される。特にpyrimethamineでは、metforminの作用（乳酸アシドーシス）やcisplatinの腎毒性が増強される。こうした排出輸送過程の相互作用を検出するため、PETなどイメージング技術が不可欠である。pyrimethamine投与時の血漿・尿検体で変動する化合物を探索した結果、<i>N</i>-methylnicotinamideをはじめ複数の化合物を同定した。一部は、基底膜側トランスポーターOCT2基質ともなることから、尿細管分泌の相互作用評価に利用することができる。内在的に存在する化合物を利用することで、プローブ薬を投与することなく、相互作用リスクを評価することが可能である。"}],"abstractLicenseFlag":"disallow"}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1420282801181572480","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"00302612"},{"@type":"NRID","@value":"1000000302612"},{"@type":"CINII_AUTHOR_ID","@value":"DA16611284"},{"@type":"URI","@value":"https://ci.nii.ac.jp/author/DA16611284#entity"},{"@type":"URI","@value":"https://viaf.org/viaf/NII%7CDA16611284"},{"@type":"NRID","@value":"9000001640779"},{"@type":"NRID","@value":"9000258577248"},{"@type":"NRID","@value":"9000401612995"},{"@type":"NRID","@value":"9000391913815"},{"@type":"NRID","@value":"9000257892608"},{"@type":"NRID","@value":"9000258574064"},{"@type":"NRID","@value":"9000009824227"},{"@type":"NRID","@value":"9000415182917"},{"@type":"NRID","@value":"9000415159748"},{"@type":"NRID","@value":"9000337087329"},{"@type":"NRID","@value":"9000005281502"},{"@type":"NRID","@value":"9000316703429"},{"@type":"NRID","@value":"9000410167334"},{"@type":"NRID","@value":"9000404638720"},{"@type":"NRID","@value":"9000415171686"},{"@type":"NRID","@value":"9000002372982"},{"@type":"NRID","@value":"9000004032068"},{"@type":"NRID","@value":"9000392712520"},{"@type":"NRID","@value":"9000278467218"},{"@type":"NRID","@value":"9000004784138"},{"@type":"NRID","@value":"9000405888396"},{"@type":"NRID","@value":"9000408487612"},{"@type":"NRID","@value":"9000415155593"},{"@type":"NRID","@value":"9000415218724"},{"@type":"NRID","@value":"9000002185625"},{"@type":"NRID","@value":"9000392702169"},{"@type":"NRID","@value":"9000283795286"},{"@type":"NRID","@value":"9000415155549"},{"@type":"NRID","@value":"9000402822792"},{"@type":"NRID","@value":"9000410317505"},{"@type":"NRID","@value":"9000415182429"},{"@type":"NRID","@value":"9000415198903"},{"@type":"NRID","@value":"9000415142437"},{"@type":"NRID","@value":"9000391913900"},{"@type":"NRID","@value":"9000257892167"},{"@type":"NRID","@value":"9000415232724"},{"@type":"NRID","@value":"9000401614344"},{"@type":"NRID","@value":"9000257889976"},{"@type":"NRID","@value":"9000257892673"},{"@type":"NRID","@value":"9000283441738"},{"@type":"NRID","@value":"9000415233061"},{"@type":"NRID","@value":"9000010520354"},{"@type":"NRID","@value":"9000257892823"},{"@type":"NRID","@value":"9000415198882"},{"@type":"NRID","@value":"9000252761503"},{"@type":"NRID","@value":"9000258577203"},{"@type":"NRID","@value":"9000297477068"},{"@type":"NRID","@value":"9000411237789"},{"@type":"NRID","@value":"9000350651524"},{"@type":"NRID","@value":"9000415142589"},{"@type":"NRID","@value":"9000415154523"},{"@type":"NRID","@value":"9000415187400"},{"@type":"NRID","@value":"9000241895179"},{"@type":"NRID","@value":"9000005240411"},{"@type":"NRID","@value":"9000252761370"},{"@type":"NRID","@value":"9000257891780"},{"@type":"NRID","@value":"9000016099016"},{"@type":"NRID","@value":"9000409884318"},{"@type":"NRID","@value":"9000405643352"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0076978"}],"foaf:name":[{"@language":"en","@value":"KUSUHARA Hiroyuki"},{"@language":"ja","@value":"楠原　 洋之"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Graduate School of Pharmaceutical Sciences, the University of Tokyo"},{"@language":"ja","@value":"東京大学大学院薬学系研究科"}]}],"publication":{"prism:publicationName":[{"@language":"en","@value":"Annual Meeting of the Japanese Society of Toxicology"},{"@language":"ja","@value":"日本毒性学会学術年会"}],"dc:publisher":[{"@language":"en","@value":"The Japanese Society of Toxicology"},{"@language":"ja","@value":"日本毒性学会"}],"prism:publicationDate":"2013","prism:volume":"40.1","prism:number":"0","prism:startingPage":"1023"},"availableAt":"2013","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=drug%20interaction","dc:title":"drug interaction"},{"@id":"https://cir.nii.ac.jp/all?q=transporter","dc:title":"transporter"},{"@id":"https://cir.nii.ac.jp/all?q=metabolite","dc:title":"metabolite"},{"@id":"https://cir.nii.ac.jp/all?q=%E8%96%AC%E7%89%A9%E7%9B%B8%E4%BA%92%E4%BD%9C%E7%94%A8","dc:title":"薬物相互作用"},{"@id":"https://cir.nii.ac.jp/all?q=%E3%83%88%E3%83%A9%E3%83%B3%E3%82%B9%E3%83%9D%E3%83%BC%E3%82%BF%E3%83%BC","dc:title":"トランスポーター"},{"@id":"https://cir.nii.ac.jp/all?q=%E4%BB%A3%E8%AC%9D%E7%89%A9","dc:title":"代謝物"}],"dataSourceIdentifier":[{"@type":"JALC","@value":"oai:japanlinkcenter.org:1003281379"},{"@type":"CIA","@value":"130004676557"}]}