PMID- 16879083
OWN - NLM
STAT- MEDLINE
DCOM- 20070410
LR  - 20151119
IS  - 0362-1642 (Print)
IS  - 0362-1642 (Linking)
VI  - 47
DP  - 2007
TI  - Idiosyncratic drug reactions: current understanding.
PG  - 513-39
AB  - Clinical characteristics and circumstantial evidence suggest that idiosyncratic 
      drug reactions are caused by reactive metabolites and are immune-mediated; 
      however, there are few definitive data and there are likely exceptions. There are 
      three principal hypotheses for how reactive metabolites might induce an 
      immune-mediated idiosyncratic reaction: the hapten hypothesis, the danger 
      hypothesis, and the PI hypothesis. It has been proposed that some idiosyncratic 
      reactions, especially those involving the liver, represent metabolic 
      idiosyncrasy; however, there are even less data to support this hypothesis. The 
      unpredictable nature of these reactions makes mechanistic studies difficult. 
      There is a very strong association with specific human leukocyte antigen (HLA) 
      genes for certain reactions, but this has only been demonstrated for very few 
      drugs. Animal models represent a very powerful tool for mechanistic studies, but 
      the number of valid models is also limited. There may be biomarkers of risk; 
      however, much more work needs to be done.
FAU - Uetrecht, Jack
AU  - Uetrecht J
AD  - Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 2S2, 
      Canada. jack.uetrecht@utoronto.ca
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Annu Rev Pharmacol Toxicol
JT  - Annual review of pharmacology and toxicology
JID - 7607088
RN  - 0 (Biomarkers)
RN  - 0 (HLA Antigens)
RN  - 0 (Pharmaceutical Preparations)
SB  - IM
MH  - *Adverse Drug Reaction Reporting Systems
MH  - Animals
MH  - *Biomarkers
MH  - *Drug-Related Side Effects and Adverse Reactions
MH  - HLA Antigens/genetics
MH  - Humans
MH  - Models, Animal
MH  - Models, Biological
MH  - Pharmaceutical Preparations/metabolism
MH  - Polymorphism, Genetic
MH  - *Predictive Value of Tests
RF  - 101
EDAT- 2006/08/02 09:00
MHDA- 2007/04/11 09:00
CRDT- 2006/08/02 09:00
PHST- 2006/08/02 09:00 [pubmed]
PHST- 2007/04/11 09:00 [medline]
PHST- 2006/08/02 09:00 [entrez]
AID - 10.1146/annurev.pharmtox.47.120505.105150 [doi]
PST - ppublish
SO  - Annu Rev Pharmacol Toxicol. 2007;47:513-39. doi: 
      10.1146/annurev.pharmtox.47.120505.105150.