{"refrec":{"BRefID":338237,"RR":"<b>Sparidans, R.W.; Rosing, H.; Hillebrand, M.J.X.; López-Lázaro, L.; Jimeno, J.M.; Manzanares, I.; van Kesteren, C.; Cvitkovic, E.; van Oosterom, A.T.; Schellens, J.H.M.; Beijnen, J.H.</b> (2001). Search for metabolites of ecteinascidin 743, a novel, marine-derived, anti-cancer agent, in man. <i>Anti-Cancer Drugs 12(8)</i>: 653-666. <a href=\"https://hdl.handle.net/10.1097/00001813-200109000-00003\" target=\"_blank\">https://hdl.handle.net/10.1097/00001813-200109000-00003</a>","BEntID":334863,"PublicFlag":1,"CheckedFlag":1,"wosflag":1,"vabbflag":0,"RefStringPartII":". <i>Anti-Cancer Drugs 12(8)</i>: 653-666. <a href=\"https://hdl.handle.net/10.1097/00001813-200109000-00003\" target=\"_blank\">https://hdl.handle.net/10.1097/00001813-200109000-00003</a>","DocTypID":8,"DocType":"Journal article","MarineFlag":1,"FreshFlag":0,"BrackishFlag":0,"TerrestrialFlag":0,"Authorstring":"Sparidans, R.W.; Rosing, H.; Hillebrand, M.J.X.; López-Lázaro, L.; Jimeno, J.M.; Manzanares, I.; van Kesteren, C.; Cvitkovic, E.; van Oosterom, A.T.; Schellens, J.H.M.; Beijnen, J.H.","OrigTitleTranslFlag":0,"Authorstringtrunc":"Sparidans, R.W. <i>et al.</i>","Englishabstract":"<span class=\"ej-keyword\" data-value=\"Ecteinascidin 743\">Ecteinascidin 743</span> (ET-743) is a potent anti-tumoral agent of a marine origin. It is currently being tested in phase II clinical trials using a 3-weekly 24-h i.v. infusion of 1500 μg/m<sup xmlns:mrws=\"http://webservices.ovid.com/mrws/1.0\">2</sup> and 3-h infusions of 1650 μg/m<sup xmlns:mrws=\"http://webservices.ovid.com/mrws/1.0\">2</sup>. Knowledge of the <span class=\"ej-keyword\" data-value=\"metabolism\">metabolism</span> of ET-743 is, however, still scarce. In the present study, a qualitative chromatographic discovery of metabolites of ET-743 in man is reported. ET-743 and its demethylated analog ET-729 were incubated at 37°C in the presence of enzyme systems, pooled human <span class=\"ej-keyword\" data-value=\"microsomes\">microsomes</span>, pooled human plasma and uridine 5′-diphosphoglucuronyltransferase, respectively, in appropriate media. Reaction products were investigated chromatographically using photodiode array and ion spray-mass spectrometric detection (LC-MS). The main reaction products in microsomal incubations of ET-743 resulted from a remarkable breakdown of the molecule. In plasma the drugs were deacetylated, and the transferase did actually yield a glucuronide of both ET-743 and ET-729. In contrast, screening of urine, plasma and bile, collected from patients treated with ET-743 at the highest dose levels, using a sensitive LC-MS assay, did not result in detection of ET-729 and metabolites which were generated <strong xmlns:mrws=\"http://webservices.ovid.com/mrws/1.0\"><em>in vitro</em></strong>. The urinary excretion of ET-743 in man was lower than 0.7% of the administered dose for a 24-h infusion.","AbstractOtherLang":null,"BibLvlCode":"AS","StandardTitle":"Search for metabolites of ecteinascidin 743, a novel, marine-derived, anti-cancer agent, in man","OrigTitleLangCode":"en","OrigTitleLangCodeExtended":"eng","OrigTitleLangID":15,"DateLastModified":{"date":"2024-12-10 01:33:17.368041","timezone_type":1,"timezone":"+01:00"},"UserAccessRight":null,"UserAccID":null,"AuthorKeywords":"ecteinascidin 729; ecteinascidin 743; high-performance liquid chromatography; metabolism; microsomes","OtherDescriptors":null,"Notes":null,"AnaPub":2001,"MonPub":null,"DateUpdate":"2021-06-01","DateCreate":"2021-05-17","SecASFANote":null,"ConfID":null,"PeerRev":1,"VlizCoreFlag":1,"WoScode":"WOS:000171164900003","VABBcode":null,"OpenAcc":0,"Handle":"10.1097/00001813-200109000-00003"},"refs":null,"anarec":{"AnaID":338237,"PubliDate":2001,"Pagination":"653-666","XtraPublOfAnaID":null,"ISBN":null,"Volume":"12","Issue":"8","BRefMon":null,"BRefMonRR":null,"BRefXtra":null,"BRefXtraRR":null,"SerBRefID":263532,"SerRR":"Anti-Cancer Drugs. 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ISSN 0959-4973; e-ISSN 1473-5741","StandardTitleSer":"Anti-Cancer Drugs","ISSN":"0959-4973","AbbrevSer":null,"StandardTitleMon":null,"StartPage":653,"Pages":14,"ToPubliDate":null,"BRefBibLvlCode":"S","SerNotes":null},"monrec":null,"serrec":null,"relations":null,"relationsRev":null,"addrec":null,"othpubs":null,"ownerships":null,"authors":[{"AutName":"Sparidans","Firstname":"Rolf","Initials":"R.W.","Affiliation":null,"Discriminator":null,"CorporateFlag":0,"BEntID":334863,"AutID":454153,"OrderNr":1,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":null,"ORCID":null,"PersID":null,"InsID":null},{"AutName":"Rosing","Firstname":"Hilde","Initials":"H.","Affiliation":null,"Discriminator":null,"CorporateFlag":0,"BEntID":334863,"AutID":242308,"OrderNr":2,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":null,"ORCID":null,"PersID":null,"InsID":null},{"AutName":"Hillebrand","Firstname":"Michel","Initials":"M.J.X.","Affiliation":null,"Discriminator":null,"CorporateFlag":0,"BEntID":334863,"AutID":242307,"OrderNr":3,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":null,"ORCID":null,"PersID":null,"InsID":null},{"AutName":"López-Lázaro","Firstname":"Luis","Initials":"L.","Affiliation":null,"Discriminator":null,"CorporateFlag":0,"BEntID":334863,"AutID":242299,"OrderNr":4,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":null,"ORCID":null,"PersID":null,"InsID":null},{"AutName":"Jimeno","Firstname":"José","Initials":"J.M.","Affiliation":null,"Discriminator":null,"CorporateFlag":0,"BEntID":334863,"AutID":454157,"OrderNr":5,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":null,"ORCID":null,"PersID":null,"InsID":null},{"AutName":"Manzanares","Firstname":"Ignacio","Initials":"I.","Affiliation":null,"Discriminator":null,"CorporateFlag":0,"BEntID":334863,"AutID":455626,"OrderNr":6,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":null,"ORCID":null,"PersID":null,"InsID":null},{"AutName":"van Kesteren","Firstname":"Charlotte","Initials":"C.","Affiliation":null,"Discriminator":null,"CorporateFlag":0,"BEntID":334863,"AutID":242295,"OrderNr":7,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":null,"ORCID":null,"PersID":null,"InsID":null},{"AutName":"Cvitkovic","Firstname":"Esteban","Initials":"E.","Affiliation":null,"Discriminator":null,"CorporateFlag":0,"BEntID":334863,"AutID":454159,"OrderNr":8,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":null,"ORCID":null,"PersID":null,"InsID":null},{"AutName":"van Oosterom","Firstname":"Allan","Initials":"A.T.","Affiliation":"Division of Oncology, University Hospital, KU Leuven","Discriminator":null,"CorporateFlag":0,"BEntID":334863,"AutID":454160,"OrderNr":9,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":"Katholieke Universiteit Leuven; 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