The purpose of this study was to examine recent findings that suggest a role for drug metabolism, namely the production of reactive metabolites, in drug hypersensitivity responses. The advent of new mass-spectrometry methods has enabled the discovery of reactive metabolites from medicines known to cause hypersensitivity responses, such as amoxicillin and nonsteroidal antiinflammatory drugs including aspirin, diclofenac, and metamizole. Recent research has shown that reactive metabolites may effectively bind plasma proteins, implying that drug metabolites may induce an immune response instead of – or in addition to – parent medicines. Because drug metabolic profiles are frequently dictated by variations in the genes that code for drug-metabolizing enzymes, it is possible that changed drug metabolism might predispose to the production of reactive drug metabolites and hence to hypersensitivity responses. In addition to the well-known efficacy of pharmacogenomics testing in type A adverse responses, our data suggest the prospective application of pharmacogenomics tests in hypersensitive adverse reactions.

A growing body of data points to a connection between genetically determined drug metabolism, changed metabolic profiles, the production of highly reactive metabolites, and haptenization. More research is needed to identify reliable biomarkers for drug-induced hypersensitivity responses.