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dc.contributor.authorHop, C.E.C.A.
dc.contributor.authorWang, Y.
dc.contributor.authorKumar, S.
dc.contributor.authorElipe, M.V.S.
dc.contributor.authorRaab, C.E.
dc.contributor.authorDean, D.C.
dc.contributor.authorPoon, G.K.
dc.contributor.authorKeohane, C.-A.
dc.contributor.authorStrauss, J.
dc.contributor.authorChiu, S.-H.L.
dc.contributor.authorCurtis, N.
dc.contributor.authorElliott, J.
dc.contributor.authorGerhard, U.
dc.contributor.authorLocker, K.
dc.contributor.authorMorrison, D.
dc.contributor.authorMortishire-Smith, R.
dc.contributor.authorThomas, S.
dc.contributor.authorWatt, A.P.
dc.contributor.authorEvans, D.C.
dc.identifier.citationHop , C E C A , Wang , Y , Kumar , S , Elipe , M V S , Raab , C E , Dean , D C , Poon , G K , Keohane , C-A , Strauss , J , Chiu , S-HL , Curtis , N , Elliott , J , Gerhard , U , Locker , K , Morrison , D , Mortishire-Smith , R , Thomas , S , Watt , A P & Evans , D C 2002 , ' Identification of metabolites of a substance P (Neurokinin 1 receptor) antagonist in rat hepatocytes and rat plasma ' , Drug Metabolism and Disposition , vol. 30 , no. 8 , pp. 937-943 .
dc.identifier.otherPURE: 940717
dc.identifier.otherPURE UUID: 2f12db72-06c2-4e6c-9fd6-c1e80020df9f
dc.identifier.otherScopus: 0036320875
dc.descriptionMEDLINE® is the source for the MeSH terms of this document.
dc.description.abstract[3R,5R,6S]-3-(2-cyclopropyloxy-5-trifluoromethoxyphenyl)-6-phenyl-1-oxa-7 -azaspiro[4.5]decane is a substance P (Neurokinin 1 receptor) antagonist. Substance P antagonists are proven in concept to have excellent potential for the treatment of major depression, and they allow superior and sustained protection from acute and delayed chemotherapy-induced emesis. The metabolism of this compound was investigated in rat hepatocytes, and circulating rat plasma metabolites were identified following oral and intravenous dosing. The turnover in rat hepatocytes within 4 h was about 30%, and the major metabolites were identified as two nitrones and a lactam associated with the piperidine ring. Although these metabolites were also observed in rat plasma, the major circulating metabolite was a keto acid following oxidative de-amination of the piperidine ring. Liquid chromatography/tandem mass spectrometry and nuclear magnetic resonance were used to confirm the structure of the latter metabolite. A mechanism leading to the formation of the keto acid metabolite has been suggested, and most intermediates were observed in rat plasma.en
dc.relation.ispartofDrug Metabolism and Disposition
dc.titleIdentification of metabolites of a substance P (Neurokinin 1 receptor) antagonist in rat hepatocytes and rat plasmaen
dc.contributor.institutionDepartment of Pharmacy
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.description.statusPeer reviewed
rioxxterms.typeJournal Article/Review

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