Drug-induced hypersensitivity reactions and pharmacogenomics: past, present and future.
Drug-induced hypersensitivity reactions represent a major concern for clinicians, patients, regulators and drug developers. Severe hypersensitivity is associated with high morbidity and mortality, it cannot be predicted from the known pharmacology of the drug and it is usually detected post-marketing when a large number of patients have been exposed to a particular drug. Recent success in developing clinically useful genetic tests that have allowed us to predict the risk of abacavir-induced hypersensitivity has helped to pave the path for a pharmacogenetic approach. However, the loop from identifying a genetic association to improving clinical outcome is still lacking for many drugs. In this commentary, we discuss the progress of hypersensitivity pharmacogenomics over the last decade and point out what remains to be done in the future. The current efforts of the international community are focused on the development of consortia, which aim to standardize disease phenotypes, but also to collect larger numbers of well-phenotyped patients and to pool biological samples through these collaborations. In addition, it is necessary to advance our knowledge of hypersensitivity mechanisms through functional studies, which will lead to the development of predictive and diagnostic tests.
Alfirevic
Ana
A
The Wolfson Centre for Personalised Medicine, Department of Pharmacology, University of Liverpool, Block A, Waterhouse Buildings, 1-5 Brownlow Street, Liverpool, L69 3GL, UK.
Pirmohamed
Munir
M
D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D004342:Drug Hypersensitivity / Q000209:etiology* / Q000235:genetics; D064420:Drug-Related Side Effects and Adverse Reactions; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism; D010597:Pharmacogenetics / Q000379:methods / Q000639:trends*; D011110:Polymorphism, Genetic; D000099227:Abacavir
D015224:Dideoxynucleosides; D006680:HLA Antigens; D004364:Pharmaceutical Preparations; D000099227:Abacavir