The purpose of this review is to examine new findings that suggest paracetamol metabolism has a role in hypersensitivity responses to this medication. Recent advances in the identification of novel paracetamol metabolites, as well as in allele frequencies and functional effects of genetic variation leading to the bioavailability of reactive paracetamol metabolites, have resulted in the identification of potential pharmacogenomic and metabolomic targets in studies looking for mechanisms involved in hypersensitivity reactions caused by this drug. The identification of metabolites with araquidonate, the identification of specific binding sequences for reactive paracetamol metabolite-protein adductives, and the frequency and functional effects studies on gene duplication or multiplication of reactive metabolites as well as complete gene deletion or deleterious mutations in genes involved in the gene formation are particularly relevant. Moreover, current data indicates that the synthesis of reactive paracetamol metabolites is based on sex, ethnic origin, or age.
There is a lot of inter-individual variation in the synthesis of reactive paracetamol metabolites, and variables that contribute to higher bioavailability of reactive paracetamol metabolites are being discovered. More study is needed to establish a connection between these variables and paracetamol-induced hypersensitivity responses.