PMID- 23768081
OWN - NLM
STAT- MEDLINE
DCOM- 20141222
LR  - 20140319
IS  - 1547-6901 (Electronic)
IS  - 1547-691X (Linking)
VI  - 11
IP  - 2
DP  - 2014 Apr-Jun
TI  - Development of a screening assay to evaluate the potential of drugs to cause 
      immune-mediated hypersensitivity reactions.
PG  - 110-5
LID - 10.3109/1547691X.2013.803269 [doi]
AB  - Evidence suggests that bio-activation of drugs to generate chemically reactive 
      metabolites (RM) that act as haptens to form immunogenic protein conjugates may 
      be an important cause of immune-mediated drug hypersensitivity reactions (IDHR). 
      Although many drugs that form RMs raise concerns about producing IDHR, standard 
      non-clinical testing methods are rarely able to identify compounds with the 
      potential to produce IDHR in humans. The objective of this study was to develop a 
      predictive assay for IDHR that involves: (1) the use of an in vitro 
      drug-metabolizing system to generate the RM that is captured by GSH, (2) 
      conjugating the RM-GSH conjugate to mouse serum albumin (MSA) by using a chemical 
      cross-linker, (3) immunization of mice with RM-GSH-MSA adducts, and (4) ex vivo 
      challenge with RM-GSH-MSA adduct and measurement of lymphocyte proliferation to 
      determine if the RM is immunogenic. The predictivity of the assay was evaluated 
      by using drugs that produce RM and have been strongly, weakly, or not associated 
      with IDHRs in the clinic. While this method requires additional validation with 
      more drugs, the results demonstrate the feasibility of identifying drugs strongly 
      associated with IDHR and the utility of the assay for rank ordering drugs with 
      respect to their potential to cause IDHR.
FAU - You, Qiang
AU  - You Q
AD  - Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado 
      Anschutz Medical Campus , Aurora, CO , USA and.
FAU - Cheng, Linling
AU  - Cheng L
FAU - Li, Dingzhou
AU  - Li D
FAU - Whritenour, Jessica
AU  - Whritenour J
FAU - Kawabata, Thomas T
AU  - Kawabata TT
FAU - Ju, Cynthia
AU  - Ju C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130614
PL  - England
TA  - J Immunotoxicol
JT  - Journal of immunotoxicology
JID - 101201960
RN  - 0 (Serum Albumin)
RN  - 33CM23913M (Carbamazepine)
RN  - GAN16C9B8O (Glutathione)
RN  - JE42381TNV (Sulfamethoxazole)
SB  - IM
MH  - Animals
MH  - Carbamazepine/*immunology
MH  - Drug Evaluation, Preclinical/*methods
MH  - Drug Hypersensitivity/*diagnosis
MH  - Female
MH  - Glutathione/metabolism
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Serum Albumin/metabolism
MH  - Sulfamethoxazole/*immunology
EDAT- 2013/06/19 06:00
MHDA- 2014/12/23 06:00
CRDT- 2013/06/18 06:00
PHST- 2013/06/18 06:00 [entrez]
PHST- 2013/06/19 06:00 [pubmed]
PHST- 2014/12/23 06:00 [medline]
AID - 10.3109/1547691X.2013.803269 [doi]
PST - ppublish
SO  - J Immunotoxicol. 2014 Apr-Jun;11(2):110-5. doi: 10.3109/1547691X.2013.803269. 
      Epub 2013 Jun 14.