2011
DOI: 10.1021/tx200337b
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Reactive Aldehyde Metabolites from the Anti-HIV Drug Abacavir: Amino Acid Adducts as Possible Factors in Abacavir Toxicity

Abstract: Abacavir is a nucleoside reverse transcriptase inhibitor marketed since 1999 for the treatment of infection with the human immunodeficiency virus type 1 (HIV). Despite its clinical efficacy, abacavir administration has been associated with serious and sometimes fatal toxic events. Abacavir has been reported to undergo bioactivation in vitro, yielding reactive species that bind covalently to human serum albumin, but the haptenation mechanism and its significance to the toxic events induced by this anti-HIV drug… Show more

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Cited by 30 publications
(37 citation statements)
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References 48 publications
(76 reference statements)
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“…The pathogenesis is related to its binding with high specificity to the HLA-B*5701 protein, changing the shape and chemistry of the antigen binding cleft. This results in a change in immunologic tolerance and the subsequent activation of abacavir-specific cytotoxic T cells, which produce the abacavir hypersensitivity syndrome (14). As such, the presence of the HLA-B*5701 gene allele is associated with elevated odds of developing a hypersensitivity reaction, and screening for this gene allele before prescribing abacavir reduces the incidence to nearly zero (15,16).…”
Section: Abacavirmentioning
confidence: 99%
“…The pathogenesis is related to its binding with high specificity to the HLA-B*5701 protein, changing the shape and chemistry of the antigen binding cleft. This results in a change in immunologic tolerance and the subsequent activation of abacavir-specific cytotoxic T cells, which produce the abacavir hypersensitivity syndrome (14). As such, the presence of the HLA-B*5701 gene allele is associated with elevated odds of developing a hypersensitivity reaction, and screening for this gene allele before prescribing abacavir reduces the incidence to nearly zero (15,16).…”
Section: Abacavirmentioning
confidence: 99%
“…1A) allowed the unequivocal identification of the N-terminal valine-abacavir adducts in three patients (two men and one woman on 600 mg abacavir once daily). This identification was based upon undistinguishable mass spectra and identical retention times, when compared with the previously prepared synthetic standard (Charneira et al, 2011). Specifically, under the chromatographic conditions used, all three positive samples and the synthetic standard displayed a signal at 10.5 min, whose MS 3 spectrum consistently presented a characteristic fragment ion at m/z 235 (Fig.…”
Section: Resultsmentioning
confidence: 94%
“…The abacavir-valine Edman adduct standard was synthesized and characterized as described in Charneira et al (2011).…”
Section: Chemicals and Standardsmentioning
confidence: 99%
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