Bioactivation to an aldehyde metabolite--possible role in the onset of toxicity induced by the anti-HIV drug abacavir

Toxicol Lett. 2014 Jan 30;224(3):416-23. doi: 10.1016/j.toxlet.2013.10.036. Epub 2013 Nov 5.


Aldehydes are highly reactive molecules, which can be generated during numerous physiological processes, including the biotransformation of drugs. Several non-P450 enzymes participate in their metabolism albeit alcohol dehydrogenase and aldehyde dehydrogenase are the ones most frequently involved in this process. Endogenous and exogenous aldehydes have been strongly implicated in multiple human pathologies. Their ability to react with biomacromolecules (e.g. proteins) yielding covalent adducts is suggested to be the common primary mechanism underlying the toxicity of these reactive species. Abacavir is one of the options for combined anti-HIV therapy. Although individual susceptibilities to adverse effects differ among patients, abacavir is associated with idiosyncratic hypersensitivity drug reactions and an increased risk of cardiac dysfunction. This review highlights the current knowledge on abacavir metabolism and discusses the potential role of bioactivation to an aldehyde metabolite, capable of forming protein adducts, in the onset of abacavir-induced toxic outcomes.

Keywords: Abacavir; Aldehyde metabolite; Cardiotoxicity; Drug bioactivation; Hypersensitivity reactions; Protein adducts.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aldehydes / metabolism*
  • Animals
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / metabolism*
  • Anti-HIV Agents / toxicity*
  • Biotransformation
  • Dideoxynucleosides / adverse effects
  • Dideoxynucleosides / metabolism*
  • Dideoxynucleosides / toxicity*
  • Drug Hypersensitivity / physiopathology
  • Drug-Related Side Effects and Adverse Reactions
  • Heart Diseases / chemically induced
  • Heart Diseases / pathology
  • Humans


  • Aldehydes
  • Anti-HIV Agents
  • Dideoxynucleosides
  • abacavir