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Evaluation of a human in vitro skin test for predicting drug hypersensitivity reactions

Lookup NU author(s): Mahid Ahmed, Louis Bibby, Laura Darby, Dr Xiao Wang, Professor Anne Dickinson

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Abstract

© 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.


Publication metadata

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

Year: 2019

Volume: 369

Pages: 39-48

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.

URL: https://doi.org/10.1016/j.taap.2019.02.005

DOI: 10.1016/j.taap.2019.02.005


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