{"@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/1390282679645335680.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.2133/dmpk.5.405"}},{"identifier":{"@type":"URI","@value":"http://www.jstage.jst.go.jp/article/dmpk1986/5/3/5_3_405/_pdf"}},{"identifier":{"@type":"NAID","@value":"130003561408"}},{"identifier":{"@type":"NAID","@value":"80005434543"}},{"identifier":{"@type":"URI","@value":"https://search.jamas.or.jp/link/ui/1993111646"}}],"dc:title":[{"@language":"en","@value":"Pharmacokinetic studies of mofezolac. II: Identification of metabolites and biotransformation of mofezolac in various animals."},{"@value":"Ｍｏｆｅｚｏｌａｃの体内動態　第２報　Ｍｏｆｅｚｏｌａｃの代謝物の同定と動物種差"}],"dc:language":"ja","description":[{"type":"abstract","notation":[{"@language":"en","@value":"<I>In vivo</I> metabolism of[3, 4-di(4-methoxyphenyl)-5-isoxazolyl]acetic acid (mofezolac) was studied in mice, rats, dogs and monkeys following intravenous injection or oral administration, and serum protein binding of mofezolac and its metabolites were studied in rats, mice, dogs, monkeys and human.<BR>Obtained results were as follows;<BR>1. Following metabolites were identified in the rat urine and bile and dog bile ; [3-(4-hydroxyphenyl)-4-(4-methoxyphenyl)-5-isoxazolyl]acetic acid (3-DM-mofezolac), [4-(4-hydroxyphenyl)-3-(4-methoxyphenyl)-5-isoxazolyl]acetic acid (4-DM-mofezolac), [3, 4-di(hydroxyphenyl)-5-isoxazolyl]acetic acid (3, 4-DM-mofezolac), 4-[4-(4-methoxyphenyl)-5-carboxymethyl-3-isoxazolyl]phenyl hydrogen sulfate (3-DM-mofezolac-sulfate), 4-[(4-hydroxyphenyl)-5-carboxymethyl-3-isoxazolyl]phenyl hydrogen sulfate (3, 4-DM-mofezolac-sulfate), β-D-glucopyranuronic acid 1-[3, 4-di(4-methoxyphenyl)-5-isoxazolyl]acetate (mofezolac-glucuronide).<BR>2. After administration to various animal species, plasma levels of mofezolac reached C<SUB>max</SUB> rapidly except monkeys. Area under concentration time curve (AUC) of mofezolac shows the species related differences with the highest AUC value found in dogs. Main metabolite in mice and monkeys plasma were 3-DM-mofezolac and 3-DM-mofezolac and 3-DM-mofezolacsulfate was found only in rats. In dogs plasma only a small quantities of metabolites were observed in the plasma. AUC of 3-DM-mofezolac-sulfate in male rats was about three times higher than female rats.<BR>3. After oral administration of mofezolac to rats, the residue of mofezolac in the stomach was about 60% at 0. 5hr, 33% at 2hr. And at 8hr, the residue in the stomach was slightly detected. In the small intestine, its content consisted mainly of 3-DM-mofezolac-sulfate. In the large intestine, the content of 3-DM-mofezolac was increased when compared with that of the small intestine.<BR>4. After oral administration, main metabolites found in the urine were 3-DM-mofezolac in mice, 3-DM-mofezolac and 3-DM-mofezolac-sulfate in rats, 3-DM-mofezolac and unchanged drug in monkeys, and unchanged drug in dogs. Total amount of urinary excretion was the lowest in dogs among examined animal species.<BR>5. In the feces after oral administration, main metabolites were 3-DM-mofezolac in mice and rats, and unchanged drug in dogs.<BR>6. Mofezolac, 3-DM-mofezolac and 4-DM mofezolac were strongly bound to serum proteins of all species studied. Mofezolac was mainly bound to albumin of human serum.<BR>7. After administration to rats, total amount excreted with bile was about 39% in bile within 24 hours. Main metabolite was 3-DM-mofezolac-sulfate."},{"@value":"ラット，マウス，サルおよびイヌに，mofezolacを経口あるいは静脈内投与し，血漿中，尿中，糞中，および胆汁中代謝物を測定した．また，血清蛋白結合性を検討したところ，次の結果が得られた．<BR>1．経口投与後のラットの尿，胆汁およびイヌの胆汁を用いて代謝物を検索した結果，次の代謝物が同定された．;[3-(4-hydroxyphenyl)-4-(4-methoxyphenyl)-5-isoxazolyl]acetic acid(3-DM-mofezolac)，[4-(4-hydroxyphenyl)-3-(4-methoxyphenyl)-5-isoxazolyl]acetic acid(4-DM-mofezolac)，[3，4-di(hydroxyphenyl)-5-isoxazolyl]acetic acid(3，4-DM-mofezolac)，4-[4-(4-methoxyphenyl)-5-carboxy-methyl-3-isoxazolyl]phenyl hydrogen sul-fate(3-DM-mofezolac-sulfate)，4-[4-(4-hydroxyphenyl)-5-carboxymethyl-3-isoxazo-1yl]phenyl hydrogen sulfate(3，4-DM-mofezolac-sulfate)，β-D-glucopyranuronic acid 1-[3，4-di(4-methoxyphenyl)-5-isoxazolyl] acetate(mofezolac-glucuronide)．<BR>2．Mofezolacの経口投与後の血漿中mofezolac濃度推移より，吸収はサルを除き速やかであったが，mofezolacのAUCには種差がみられイヌが最も高かった．血漿中主代謝物についてみると，マウスおよびサルでは3-DM-mofez-olac，ラットでは3-DM-mofezolacおよび3-DM-mofezolac-sulfateであり，イヌにおいてはmofezolacが大部分を占め，代謝物はぎわめて低かった．また，雌性ラットにおいては雄性ラットに比べ3-DM-mofezolac-sulfateのAUCは約1/3であった．<BR>3．Mofezolac経口投与後のラットの胃内には，ほとんどがmofezolacとして存在しており，0．5hrで約60%，2hrで約33%認められたが，8hrではわずかであった．小腸内においては，主として3-DM-mofezolac-sulfateであり，大腸内においては3-DM-mofezolac-su-lfateもみられたが，3-DM-mofezolacの存在量が増加した．<BR>4．Mofezolac経口投与後の尿中には，マウスではほとんどが3-DM-mofezolacとして，ラットでは3-DM-mofezolac，次いで3-DM-mofezolac-sulfate，サルでは3-DM-mofezolac，次いでmofezolacが，イヌではほとんどがmofezolacとして排泄された．測定代謝物の尿中総排泄率はイヌが最も低かった．<BR>5．Mofezolac経口投与後，糞中にはマウス，ラットでは3-DM-mofezolac，イヌではmofezolacとして排泄された．<BR>6．Mofezolacおよび代謝物3-DM-mofez-olac，4-DM-mofezolacぱ，いずれの動物種の血清蛋白に対しても高い結合率を示した．ヒト血清中のmofezolacの結合画分はアルブミンであった．7．Mofezolacをラットに経口投与後24hrまでに胆汁中にぱ約39%が排泄された．最も多く排泄されたのは3-DM-mofezolac-sulfateであった．"}],"abstractLicenseFlag":"disallow"}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1410282679645335683","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000253264131"}],"foaf:name":[{"@language":"en","@value":"SHINDO Takashi"},{"@language":"ja","@value":"新藤 恭司"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Biological Research Laboratory, Taiho Pharmaceutical Co., Ltd."},{"@language":"ja","@value":"大鵬薬品工業株式会社開発研究所"}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679645335681","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000253264132"}],"foaf:name":[{"@language":"en","@value":"KAWAUCHI Takashi"},{"@language":"ja","@value":"川内 隆史"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Biological Research Laboratory, Taiho Pharmaceutical Co., Ltd."},{"@language":"ja","@value":"大鵬薬品工業株式会社開発研究所"}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679645335684","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000253264133"}],"foaf:name":[{"@language":"en","@value":"MASUDA Hirotoshi"},{"@language":"ja","@value":"増田 啓年"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Biological Research Laboratory, Taiho Pharmaceutical Co., Ltd."},{"@language":"ja","@value":"大鵬薬品工業株式会社開発研究所"}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679645335680","@type":"Researcher","foaf:name":[{"@language":"en","@value":"SUZUKI Takashi"},{"@language":"ja","@value":"鈴木 高志"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Biological Research Laboratory, Taiho Pharmaceutical Co., Ltd."},{"@language":"ja","@value":"大鵬薬品工業株式会社開発研究所"}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679645335686","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000253264135"}],"foaf:name":[{"@language":"en","@value":"MINAMI Yoshinori"},{"@language":"ja","@value":"南 慶典"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Biological Research Laboratory, Taiho Pharmaceutical Co., Ltd."},{"@language":"ja","@value":"大鵬薬品工業株式会社開発研究所"}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679645335685","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000253264136"}],"foaf:name":[{"@language":"en","@value":"MANIWA Madoka"},{"@language":"ja","@value":"真庭 まどか"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Biological Research Laboratory, Taiho Pharmaceutical Co., Ltd."},{"@language":"ja","@value":"大鵬薬品工業株式会社開発研究所"}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679645335682","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000253264137"}],"foaf:name":[{"@language":"en","@value":"KAWAGUCHI Yasuro"},{"@language":"ja","@value":"川口 安郎"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Biological Research Laboratory, Taiho Pharmaceutical Co., Ltd."},{"@language":"ja","@value":"大鵬薬品工業株式会社開発研究所"}]}],"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":"1990","prism:volume":"5","prism:number":"3","prism:startingPage":"405","prism:endingPage":"427"},"reviewed":"false","url":[{"@id":"http://www.jstage.jst.go.jp/article/dmpk1986/5/3/5_3_405/_pdf"},{"@id":"https://search.jamas.or.jp/link/ui/1993111646"}],"availableAt":"1990","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=mofezolac","dc:title":"mofezolac"},{"@id":"https://cir.nii.ac.jp/all?q=analgesic","dc:title":"analgesic"},{"@id":"https://cir.nii.ac.jp/all?q=metabolism","dc:title":"metabolism"},{"@id":"https://cir.nii.ac.jp/all?q=oral%20administration","dc:title":"oral administration"},{"@id":"https://cir.nii.ac.jp/all?q=intravenous","dc:title":"intravenous"},{"@id":"https://cir.nii.ac.jp/all?q=administration","dc:title":"administration"},{"@id":"https://cir.nii.ac.jp/all?q=animal%20difference","dc:title":"animal difference"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360290617673125248","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Physiologically Based Pharmacokinetic Models Predicting Renal and Hepatic Concentrations of Industrial Chemicals after Virtual Oral Doses in Rats"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679646772352","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Metabolism of a New Antiplatelet Agent, Ethyl 2-(4, 5-bis (4-methoxyphenyl) thiazol-2-yl) pyrrol-1-ylacetate (KBT-3022), in Rats, Mice, Dogs and Humans."},{"@value":"新規抗血小板薬Ｅｔｈｙｌ　２‐［４，５‐ｂｉｓ（４‐ｍｅｔｈｏｘｙｐｈｅｎｙｌ）ｔｈｉａｚｏｌ‐２‐ｙｌ］ｐｙｒｒｏｌ‐１‐ｙｌａｃｅｔａｔｅ（ＫＢＴ‐３０２２）のラット，マウス，イヌおよびヒトにおける代謝"}]}],"dataSourceIdentifier":[{"@type":"JALC","@value":"oai:japanlinkcenter.org:0007686571"},{"@type":"CROSSREF","@value":"10.2133/dmpk.5.405"},{"@type":"CIA","@value":"130003561408"},{"@type":"CIA","@value":"80005434543"},{"@type":"CROSSREF","@value":"10.1021/acs.chemrestox.0c00009_references_DOI_YIrYNJuGV2aoKsPMASR8s4fKhuS"}]}