Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.17/1774
Título: Monitoring Abacavir Bioactivation in Humans: Screening for an Aldehyde Metabolite
Autor: Grilo, N
Antunes, A
Caixas, U
Marinho, A
Charneira, C
Oliveira, MC
Monteiro, E
Marques, MM
Pereira, S
Palavras-chave: CHLC MED
Aldeídos
Marcadores Biológicos
Biotransformação
Didesoxinucleosídeos
Monitorização de Medicamentos
Hemoglobinas
Proteínas
Espectrometria de Massas por Ionização por Electrospray
Anti-Retrovirais
Infecção por HIV
Espectrometria de Massas em Tandem
Metabolismo
Efeitos Adversos
Data: 2013
Editora: Elsevier
Citação: Toxicol Lett. 2013 May 10;219(1):59-64
Resumo: The 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.
Peer review: yes
URI: http://hdl.handle.net/10400.17/1774
Aparece nas colecções:MED - Artigos

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