PMID- 29405076
OWN - NLM
STAT- MEDLINE
DCOM- 20190124
LR  - 20190124
IS  - 1746-045X (Electronic)
IS  - 1746-0441 (Linking)
VI  - 13
IP  - 5
DP  - 2018 May
TI  - Tools to investigate and avoid drug-hypersensitivity in drug development.
PG  - 425-433
LID - 10.1080/17460441.2018.1437141 [doi]
AB  - 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.
FAU - Corsini, Emanuela
AU  - Corsini E
AUID- ORCID: 0000-0002-6927-5956
AD  - a Laboratory of Toxicology, Department of Environmental Science and Policy ,
      Universita degli Studi di Milano , Milan , Italy.
FAU - Casula, Manuela
AU  - Casula M
AUID- ORCID: 0000-0002-5124-5361
AD  - b Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of
      Pharmacological and Biomolecular Sciences , University of Milan , Milan , Italy.
FAU - Tragni, Elena
AU  - Tragni E
AUID- ORCID: 0000-0001-9932-415X
AD  - b Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of
      Pharmacological and Biomolecular Sciences , University of Milan , Milan , Italy.
FAU - Galbiati, Valentina
AU  - Galbiati V
AUID- ORCID: 0000-0003-3380-1501
AD  - a Laboratory of Toxicology, Department of Environmental Science and Policy ,
      Universita degli Studi di Milano , Milan , Italy.
FAU - Pallardy, Marc
AU  - Pallardy M
AUID- ORCID: 0000-0001-8869-0365
AD  - c Inflammation, Chemokines and Immunopathology , INSERM UMR 996, Univ Paris-Sud, 
      Universite Paris-Saclay , Chatenay-Malabry , France.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20180206
PL  - England
TA  - Expert Opin Drug Discov
JT  - Expert opinion on drug discovery
JID - 101295755
SB  - IM
MH  - Animals
MH  - Drug Development/*methods
MH  - Drug Evaluation, Preclinical/methods
MH  - Drug Hypersensitivity/*diagnosis/immunology/prevention & control
MH  - Drug-Related Side Effects and Adverse Reactions/*diagnosis/immunology/prevention 
      & control
MH  - Humans
MH  - Toxicity Tests/methods
OTO - NOTNLM
OT  - *Drug adverse reaction
OT  - *hypersensitivity
OT  - *in vitro
OT  - *in vivo
EDAT- 2018/02/07 06:00
MHDA- 2019/01/25 06:00
CRDT- 2018/02/07 06:00
PHST- 2018/02/07 06:00 [pubmed]
PHST- 2019/01/25 06:00 [medline]
PHST- 2018/02/07 06:00 [entrez]
AID - 10.1080/17460441.2018.1437141 [doi]
PST - ppublish
SO  - Expert Opin Drug Discov. 2018 May;13(5):425-433. doi:
      10.1080/17460441.2018.1437141. Epub 2018 Feb 6.