{"@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/1390282679609496192.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1248/bpb.b15-00293"}},{"identifier":{"@type":"PMID","@value":"26228628"}},{"identifier":{"@type":"NDL_BIB_ID","@value":"026763632"}},{"identifier":{"@type":"URI","@value":"http://id.ndl.go.jp/bib/026763632"}},{"identifier":{"@type":"URI","@value":"https://ndlsearch.ndl.go.jp/books/R000000004-I026763632"}},{"identifier":{"@type":"URI","@value":"https://www.jstage.jst.go.jp/article/bpb/38/10/38_b15-00293/_pdf"}},{"identifier":{"@type":"NAID","@value":"130005101593"}},{"identifier":{"@type":"URI","@value":"https://search.jamas.or.jp/link/ui/2016175311"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@language":"en","@value":"Pharmacokinetics and Brain Distribution and Metabolite Identification of Coptisine, a Protoberberine Alkaloid with Therapeutic Potential for CNS Disorders, in Rats"}],"dc:language":"en","description":[{"type":"abstract","notation":[{"@language":"en","@value":"Coptisine (COP), a protoberberine alkaloid (PBA) from Chinese medicinal plants (such as family Berberidaceae), may be useful for improving central nervous system disorders. However, its pharmacokinetics, disposition and metabolism are not well defined. In the present study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for the analysis of COP in biological samples. To better understand its <i>in vivo</i> pharmacological activities, COP concentrations in rat plasma were determined after oral (50 mg/kg) and intravenous administration (10 mg/kg). For the brain distribution study, the concentration of COP in five different regions was examined after intravenous administration at 10 mg/kg. Pharmacokinetic parameters from the COP concentration–time profiles in plasma and brain, and the brain-to-plasma coefficient (<i>K</i><sub>p, brain</sub>) were calculated by non-compartmental analysis. The metabolites of COP in rats <i>in vivo</i> and <i>in vitro</i> (urine, bile, liver microsomes and intestinal bacteria incubation) were also identified. Seventeen metabolites, including 11 unconjugated metabolites formed by hydroxylation, hydrogenation, demethylation, dehydrogenation, demethylation, and 6 glucuronide and sulfate conjugates were identified for the first time. The results suggested that COP had low oral bioavailability of 8.9% and a short (plasma) half-life (<i>T</i><sub>1/2</sub>=0.71 h) in rats. After intravenous administration, it quickly crossed the blood–brain barrier, accumulating at higher concentrations and then was slowly eliminated from different brain regions. Moreover, COP was transformed into metabolites through multiple metabolic pathways <i>in vivo</i> and <i>in vitro</i>. These results should help to promote further research on COP and contribute to clarifying the metabolic pathways of PBAs."}],"abstractLicenseFlag":"disallow"}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1410282679609496193","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000307261547"}],"foaf:name":[{"@language":"en","@value":"Su Jin"}],"jpcoar:affiliationName":[{"@language":"en","@value":"School of Chinese Materia Medica, Beijing University of Chinese Medicine"},{"@language":"en","@value":"School of Pharmacy, Jiamusi University"}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679609496196","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000307261548"}],"foaf:name":[{"@language":"en","@value":"Miao Qing"}],"jpcoar:affiliationName":[{"@language":"en","@value":"School of Chinese Materia Medica, Beijing University of Chinese Medicine"}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679609496192","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000307261549"}],"foaf:name":[{"@language":"en","@value":"Miao Peipei"}],"jpcoar:affiliationName":[{"@language":"en","@value":"School of Chinese Materia Medica, Beijing University of Chinese Medicine"}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679609496195","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000307261550"}],"foaf:name":[{"@language":"en","@value":"Zhao Yuanyuan"}],"jpcoar:affiliationName":[{"@language":"en","@value":"School of Chinese Materia Medica, Beijing University of Chinese Medicine"}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679609496198","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000307261551"}],"foaf:name":[{"@language":"en","@value":"Zhang Yuanyuan"}],"jpcoar:affiliationName":[{"@language":"en","@value":"School of Chinese Materia Medica, Beijing University of Chinese Medicine"}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679609496194","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000307261552"}],"foaf:name":[{"@language":"en","@value":"Chen Ning"}],"jpcoar:affiliationName":[{"@language":"en","@value":"School of Chinese Materia Medica, Beijing University of Chinese Medicine"}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679609496199","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000307261553"}],"foaf:name":[{"@language":"en","@value":"Zhang Yujie"}],"jpcoar:affiliationName":[{"@language":"en","@value":"School of Chinese Materia Medica, Beijing University of Chinese Medicine"}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679609496197","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000307261554"}],"foaf:name":[{"@language":"en","@value":"Ma Shuangcheng"}],"jpcoar:affiliationName":[{"@language":"en","@value":"National Institutes for Food and Drug Control"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"09186158"},{"@type":"EISSN","@value":"13475215"},{"@type":"NDL_BIB_ID","@value":"000000153250"},{"@type":"ISSN","@value":"09186158"},{"@type":"LISSN","@value":"09186158"},{"@type":"NCID","@value":"AA10885497"}],"prism:publicationName":[{"@language":"ja","@value":"Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ"},{"@language":"en","@value":"Biological and Pharmaceutical Bulletin"},{"@language":"en","@value":"Biological & Pharmaceutical Bulletin"},{"@language":"en","@value":"Biol. Pharm. Bull."},{"@language":"ja","@value":"Ｂｉｏｌ．　Ｐｈａｒｍ．　Ｂｕｌｌ．"}],"dc:publisher":[{"@language":"en","@value":"The Pharmaceutical Society of Japan"},{"@language":"ja","@value":"公益社団法人 日本薬学会"}],"prism:publicationDate":"2015","prism:volume":"38","prism:number":"10","prism:startingPage":"1518","prism:endingPage":"1528"},"reviewed":"false","url":[{"@id":"http://id.ndl.go.jp/bib/026763632"},{"@id":"https://ndlsearch.ndl.go.jp/books/R000000004-I026763632"},{"@id":"https://www.jstage.jst.go.jp/article/bpb/38/10/38_b15-00293/_pdf"},{"@id":"https://search.jamas.or.jp/link/ui/2016175311"}],"availableAt":"2015","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=coptisine","dc:title":"coptisine"},{"@id":"https://cir.nii.ac.jp/all?q=pharmacokinetics","dc:title":"pharmacokinetics"},{"@id":"https://cir.nii.ac.jp/all?q=brain%20distribution","dc:title":"brain distribution"},{"@id":"https://cir.nii.ac.jp/all?q=metabolite","dc:title":"metabolite"},{"@id":"https://cir.nii.ac.jp/all?q=LC-MS/MS","dc:title":"LC-MS/MS"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050850247205824000","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Anti-malarial activity of traditional Kampo medicine Coptis rhizome extract and its major active compounds"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011143695104000","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Structure and function of the blood–brain barrier"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011144754048768","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Use of Plasma and Brain Unbound Fractions to Assess the Extent of Brain Distribution of 34 Drugs: Comparison of Unbound Concentration Ratios to in Vivo P-Glycoprotein Efflux 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Rats"}]},{"@id":"https://cir.nii.ac.jp/crid/1363670321328022528","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Metabolic profiling analysis of berberine, palmatine, jatrorrhizine, coptisine and epiberberine in zebrafish by ultra-high performance liquid chromatography coupled with LTQ Orbitrap mass spectrometer"}]},{"@id":"https://cir.nii.ac.jp/crid/1363951795615922048","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"D1 and D2 dopamine receptors differentially regulate c-fos expression in striatonigral and striatopallidal neurons"}]},{"@id":"https://cir.nii.ac.jp/crid/1363951795732561408","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Effects of borneol on the pharmacokinetics of geniposide in cortex, hippocampus, hypothalamus and striatum of conscious rat by simultaneous brain microdialysis coupled with 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