Tools to investigate and avoid drug-hypersensitivity in drug development.

Tools to investigate and avoid drug-hypersensitivity in drug development.

Expert Opin Drug Discov. 2018 Feb 06;:1-9

Authors: Corsini E, Casula M, Tragni E, Galbiati V, Pallardy M

Abstract
INTRODUCTION: Drug hypersensitivity reactions (DHRs) are common adverse effects of pharmaceuticals that clinically resemble allergies, and which are becoming an important burden to healthcare systems. Alongside accurate diagnostic techniques, tools which can predict potential drug-inducing hypersensitivity reactions in the pre-clinical phase are critical. Despite the important adverse reactions linked to immune-mediated hypersensitivity, at present, there are no validated or required in vivo or in vitro methods to screen the sensitizing potential of drugs and their metabolites in the pre-clinical phase. Areas covered: Enhanced prediction in preclinical safety evaluation is extremely important. The purpose of this review is to assess the state of the art of tools available to assess the allergenic potential of drugs and to highlight our current understanding of the molecular mechanisms underlying inappropriate immune activation. Expert opinion: The knowledge that allergenic drugs share common mechanisms of immune cell activation with chemical allergens, and of the definition of the mechanistic pathway to adverse outcomes, can enhance targeting toxicity testing in drug development and hazard assessment of hypersensitivity. Additional efforts and extensive resources are necessary to improve preclinical testing methodologies, including optimization, better design and interpretation of data.

PMID: 29405076 [PubMed - as supplied by publisher]

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