Metabolism of Drugs by Activated Leukocytes: Implications for Drug-Induced Lupus and Other Drug Hypersensitivity Reactions

  • Jack Uetrecht
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 283)


Adverse drug reactions represent a serious medical problem. Idiosyncratic reactions are especially disconcerting because of their unpredictable nature which makes them difficult to prevent, and because they are associated with a relatively high mortality rate. General agreement on the definition of an idiosyncratic reaction is lacking, but the term will be used to mean a reaction that does not occur in most patients given the drug even at a high dose, and one that does not represent a manifestation of the known pharmacological effects of a drug. The mechanism of idiosyncratic reactions is unknown, and several different mechanisms may be involved. The study of idiosyncratic reactions is very difficult because they do not occur in most patients, and by extension, they do not occur in most animals even at a very high dose. Thus, there are very few animal models of idiosyncratic reactions which would permit careful investigation of their mechanism. It is probable that if enough different types of animals were tried, an animal model could be developed, but it might take many thousands of different species before one was found that would have a reaction similar to the rare individual human that has a reaction. It should be noted that, although a specific adverse reaction to a specific drug may be rare, there are enough different drugs being given to enough different individuals that idiosyncratic reactions are very common.


Antinuclear Antibody Covalent Binding Histone Protein Reactive Metabolite Thyroid Peroxidase 
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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Jack Uetrecht
    • 1
  1. 1.Faculties of Pharmacy and Medicine University of Toronto and Sunnybrook Medical Centre Centre for Drug Safety ResearchUniversity of TorontoTorontoCanada

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