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

被引:23
作者
Elzagallaai, Abdelbaset A. [1 ]
Rieder, Michael J. [1 ,2 ,3 ,4 ]
机构
[1] Univ Western Ontario, Dept Pediat, Schulich Sch Med & Dent, London, ON N6A 3K7, Canada
[2] Univ Western Ontario, Dept Med, Schulich Sch Med & Dent, London, ON, Canada
[3] Univ Western Ontario, Dept Physiol & Pharmacol, Schulich Sch Med & Dent, London, ON, Canada
[4] Univ Western Ontario, Schulich Sch Med & Dent, CIHR GSK Chair Pediat Clin Pharmacol, London, ON, Canada
关键词
adverse drug events; adverse drug reactions; drug allergy; idiosyncratic drug reactions; in vitro diagnosis; LYMPHOCYTE-TRANSFORMATION TEST; BASOPHIL ACTIVATION TEST; STEVENS-JOHNSON SYNDROME; ANTICONVULSANT HYPERSENSITIVITY SYNDROME; INDUCED LIVER-INJURY; TOXICITY ASSAY IPTA; T-CELLS; REVISED NOMENCLATURE; ERYTHEMA MULTIFORME; PREDICTIVE-VALUE;
D O I
10.1111/bcp.12505
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:889 / 900
页数:12
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