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Monitoring Abacavir Bioactivation in Humans: Screening for an Aldehyde Metabolite

dc.contributor.authorGrilo, N
dc.contributor.authorAntunes, A
dc.contributor.authorCaixas, U
dc.contributor.authorMarinho, A
dc.contributor.authorCharneira, C
dc.contributor.authorOliveira, MC
dc.contributor.authorMonteiro, E
dc.contributor.authorMarques, MM
dc.contributor.authorPereira, S
dc.date.accessioned2014-04-08T11:28:53Z
dc.date.available2014-04-08T11:28:53Z
dc.date.issued2013
dc.description.abstractThe anti-HIV drug abacavir is associated with idiosyncratic hypersensitivity reactions and cardiotoxicity. Although the mechanism underlying abacavir-toxicity is not fully understood, drug bioactivation to reactive metabolites may be involved. This work was aimed at identifying abacavir-protein adducts in the hemoglobin of HIV patients as biomarkers of abacavir bioactivation and protein modification. The protocol received prior approval from the Hospital Ethics Committee, patients gave their written informed consent and adherence was controlled through a questionnaire. Abacavir-derived Edman adducts with the N-terminal valine of hemoglobin were analyzed by an established liquid chromatography-electrospray ionization-tandem mass spectrometry method. Abacavir-valine adducts were detected in three out of ten patients. This work represents the first evidence of abacavir-protein adduct formation in humans. The data confirm the ability of abacavir to modify self-proteins and suggest that the molecular mechanism(s) of some abacavir-induced adverse reactions may require bioactivation.por
dc.identifier.citationToxicol Lett. 2013 May 10;219(1):59-64por
dc.identifier.urihttp://hdl.handle.net/10400.17/1774
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherElsevierpor
dc.subjectCHLC MEDpor
dc.subjectAldeídospor
dc.subjectMarcadores Biológicospor
dc.subjectBiotransformaçãopor
dc.subjectDidesoxinucleosídeospor
dc.subjectMonitorização de Medicamentospor
dc.subjectHemoglobinaspor
dc.subjectProteínaspor
dc.subjectEspectrometria de Massas por Ionização por Electrospraypor
dc.subjectAnti-Retroviraispor
dc.subjectInfecção por HIVpor
dc.subjectEspectrometria de Massas em Tandempor
dc.subjectMetabolismopor
dc.subjectEfeitos Adversospor
dc.titleMonitoring Abacavir Bioactivation in Humans: Screening for an Aldehyde Metabolitepor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage64por
oaire.citation.startPage59por
oaire.citation.titleToxicology Letterspor
rcaap.rightsopenAccesspor
rcaap.typearticlepor

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