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Lookup NU author(s): Mahid Ahmed,
Dr Xiao WangORCiD,
Professor Anne Dickinson
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© 2019 Elsevier Inc. The occurrence of drug hypersensitivity reactions (DHRs) following administration of low molecular weight (LMW) drugs is an important health concern. However, in vivo animal models which could be used as tools for the prediction of DHRs are lacking. As a result, research has focused on development of in vitro tools for predicting DHRs. In this study a novel human in vitro pre-clinical skin explant test was used to predict T cell-mediated hypersensitivity responses induced by LMW drugs. Responses in the skin explant test for 12 LMW drugs associated with T cell-mediated hypersensitivity in the clinic (abacavir, amoxicillin, carbamazepine, diclofenac, lamotrigine, lapatinib, lumiracoxib, nevirapine, ofloxacin, phenytoin, propranolol, sulfamethoxazole) were compared with responses for 5 drugs with few/no reports of T cell-mediated hypersensitivity reactions (acetaminophen, cimetidine, flecainide, metformin, verapamil). Changes in skin histology following in vitro exposure to the drugs as well as T cell proliferation and interferon gamma (IFNγ) production were studied. The results of the skin explant assays showed a good positive correlation (r = 0.77, p <.001) between the test outcome (prediction of positive or negative) and the clinical classification of the tested drugs. The T cell proliferation assay showed a correlation of r = 0.60 (p <.01) and the IFNγ assay r = 0.51 (p <.04). The data suggest that the skin explant model could be a useful tool to predict the potential of LMW drugs to induce DHRs.
Author(s): Ahmed SS, Whritenour J, Ahmed MM, Bibby L, Darby L, Wang XN, Watson J, Dickinson AM
Publication type: Article
Publication status: Published
Journal: Toxicology and Applied Pharmacology
Print publication date: 15/04/2019
Online publication date: 12/02/2019
Acceptance date: 11/02/2019
ISSN (print): 0041-008X
ISSN (electronic): 1096-0333
Publisher: Academic Press Inc.
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