Evidence of haptenation upon bioactivation of the anti-HIV drug abacavir to a reactive aldehyde in vivo

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

The benefits of cART have revolutionized the life expectancy of HIV-infected patients, though treatment-associated toxicity is frequently observed. Abacavir is an NRTI associated with acute toxic events, such as hypersensitivity reactions, which often lead to drug discontinuation. Moreover, an association between long-term abacavir use and increased risk of myocardial infarction, though still controversial, has been reported. Bioactivation to a reactive aldehyde, capable of modifying self-proteins, is thought to be involved at the onset of these adverse reactions. We have proposed that a conjugated aldehyde is the electrophilic intermediate primarily responsible for reaction with the N-terminal valine of hemoglobin via Schiff base formation in vitro, but so far this reactive metabolite has eluded detection in vivo. As such, the aim of the present work was to obtain evidence of abacavir bioactivation to a reactive aldehyde metabolite in vivo, both in an animal model and in man. Número de acesso: WOS:000322821600030
Original languageUnknown
Title of host publicationROCEEDINGS OF THE 6TH EUROPEAN CONGRESS OF PHARMACOLOGY
Pages155-158
Publication statusPublished - 1 Jan 2013
Event6th European Congress of Pharmacology Local: Granada, SPAIN Data: JUL 17-20, 2012 Patrocinador(es): EPHAR -
Duration: 1 Jan 2012 → …

Conference

Conference6th European Congress of Pharmacology Local: Granada, SPAIN Data: JUL 17-20, 2012 Patrocinador(es): EPHAR
Period1/01/12 → …

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