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- W1532674929 abstract "BACKGROUND AND PURPOSE The aim of this study was to obtain evidence for the activation of the nucleoside reverse transcriptase inhibitor abacavir to reactive aldehyde metabolites in vivo . Protein haptenation by these reactive metabolites may be a factor in abacavir‐induced toxic events. EXPERIMENTAL APPROACH The formation of N ‐terminal valine adducts from the abacavir‐derived aldehydes was investigated in the haemoglobin of Wistar rats treated with eight daily doses (120 mg·kg −1 ) of abacavir. The analyses were conducted by high‐performance liquid chromatography‐electrospray ionization‐tandem mass spectrometry upon comparison with synthetic standards. KEY RESULTS An N ‐terminal valine haemoglobin adduct derived from an α,β‐unsaturated aldehyde metabolite of abacavir was identified in vivo for the first time. CONCLUSIONS AND IMPLICATIONS This preliminary work on abacavir metabolism provides the first unequivocal evidence for the formation of an α,β‐unsaturated aldehyde metabolite in vivo and of its ability to form haptens with proteins. The methodology described herein can be used to assess the formation of this metabolite in human samples and has the potential to become a valuable pharmacological tool for mechanistic studies of abacavir toxicity. In fact, the simplicity of the method suggests that the abacavir adduct with the N ‐terminal valine of haemoglobin could be used to investigate abacavir‐induced toxicity for accurate risk/benefit estimations." @default.
- W1532674929 created "2016-06-24" @default.
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- W1532674929 date "2012-10-19" @default.
- W1532674929 modified "2023-10-18" @default.
- W1532674929 title "<i>N</i>-terminal valine adduct from the anti-HIV drug abacavir in rat haemoglobin as evidence for abacavir metabolism to a reactive aldehyde<i>in vivo</i>" @default.
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- W1532674929 doi "https://doi.org/10.1111/j.1476-5381.2012.02079.x" @default.
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