In vitro testing for diagnosis of idiosyncratic adverse drug reactions: Implications for pathophysiology

• Published in: British journal of clinical pharmacology Vol. 80; no. 4; pp. 889 - 900
• Main Authors: Elzagallaai, Abdelbaset A., Rieder, Michael J.
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Ltd 01.10.2015
• Subjects: adverse drug events; adverse drug reactions; drug allergy; Drug-Related Side Effects and Adverse Reactions - diagnosis; Humans; idiosyncratic drug reactions; in vitro diagnosis; In Vitro Techniques - methods; In Vitro Techniques - standards; Themed Section - Adverse Drug Reactions; in vitro diagnosis; adverse drug events; adverse drug reactions; drug allergy; idiosyncratic drug reactions
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/bcp.12505

Idiosyncratic drug reactions (IDRs) represent a major health problem, as they are unpredictable, often severe and can be life threatening. The low incidence of IDRs makes their detection during drug development stages very difficult causing many post‐marketing drug withdrawals and black box warnings. The fact that IDRs are always not predictable based on the drug's known pharmacology and have no clear dose–effect relationship with the culprit drug renders diagnosis of IDRs very challenging, if not impossible, without the aid of a reliable diagnostic test. The drug provocation test (DPT) is considered the gold standard for diagnosis of IDRs but it is not always safe to perform on patients. In vitro tests have the advantage of bearing no potential harm to patients. However, available in vitro tests are not commonly used clinically because of lack of validation and their complex and expensive procedures. This review discusses the current role of in vitro diagnostic testing for diagnosis of IDRs and gives a brief account of their technical and mechanistic aspects. Advantages, disadvantages and major challenges that prevent these tests from becoming mainstream diagnostic tools are also discussed here.