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.

Tools to investigate and avoid drug-hypersensitivity in drug development / E. Corsini, M. Casula, E. Tragni, V. Galbiati, M. Pallardy. - In: EXPERT OPINION ON DRUG DISCOVERY. - ISSN 1746-0441. - 13:5(2018 May 04), pp. 425-433. [10.1080/17460441.2018.1437141]

Tools to investigate and avoid drug-hypersensitivity in drug development

E. Corsini
;
M. Casula;E. Tragni;V. Galbiati;
2018

Abstract

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.
drug adverse reaction; hypersensitivity; in vitro; in vivo
Settore BIO/14 - Farmacologia
6-feb-2018
Article (author)
File in questo prodotto:
File Dimensione Formato  
Tools to investigate and avoid drug hypersensitivity in drug development.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 1.48 MB
Formato Adobe PDF
1.48 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/551296
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 6
social impact