title: Drug metabolism and hypersensitivity reactions to drugs.
abstract: OBJECTIVE
  The aim of the present review was to discuss recent advances supporting a role of drug metabolism, and particularly of the generation of reactive metabolites, in hypersensitivity reactions to drugs.
  
  
  RESULTS
  The development of novel mass-spectrometry procedures has allowed the identification of reactive metabolites from drugs known to be involved in hypersensitivity reactions, including amoxicillin and nonsteroidal antiinflammatory drugs such as aspirin, diclofenac or metamizole. Recent studies demonstrated that reactive metabolites may efficiently bind plasma proteins, thus suggesting that drug metabolites, rather than - or in addition to - parent drugs, may elicit an immune response. As drug metabolic profiles are often determined by variability in the genes coding for drug-metabolizing enzymes, it is conceivable that an altered drug metabolism may predispose to the generation of reactive drug metabolites and hence to hypersensitivity reactions. These findings support the potential for the use of pharmacogenomics tests in hypersensitivity (type B) adverse reactions, in addition to the well known utility of these tests in type A adverse reactions.
  
  
  CONCLUSIONS
  Growing evidence supports a link between genetically determined drug metabolism, altered metabolic profiles, generation of highly reactive metabolites and haptenization. Additional research is required to developing robust biomarkers for drug-induced hypersensitivity reactions.
authors.affiliation: aDepartment of Pharmacology, University of Extremadura, Cáceres bResearch Laboratory, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain.
authors.forename: José A G
authors.initials: JA
authors.lastname: Agúndez
authors.forename: Cristobalina
authors.initials: C
authors.lastname: Mayorga
authors.forename: Elena
authors.initials: E
authors.lastname: García-Martin
mesh_terms: D000658:Amoxicillin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism; D004342:Drug Hypersensitivity / Q000235:genetics / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D010597:Pharmacogenetics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001798:Blood Proteins; D000658:Amoxicillin