Research Topics
| J P UetrechtSummaryAffiliation: University of Toronto Country: Canada Publications
| Collaborators
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Detail Information
Publications
Immunoallergic drug-induced liver injury in humansJack Uetrecht
Leslie Dan Faculty of Pharmacy, University of Toronto, Ontario, Canada
Semin Liver Dis 29:383-92. 2009..This is likely responsible for the interindividual differences in susceptibility and outcome noted in human DILI...- Structural features associated with reactive metabolite formation in clozapine analoguesJ Uetrecht
Faculty of Pharmacy and Medicine, University of Toronto, Canada
Chem Biol Interact 104:117-29. 1997..If such reactive metabolites are responsible for drug-induced agranulocytosis, it should be possible to use such a simple screening method to test drugs at an early stage in their development for the potential to induce agranulocytosis... - Role of drug metabolism for breaking tolerance and the localization of drug hypersensitivityJack Uetrecht
University of Toronto, Faculty of Pharmacy, 19 Russell St, Toronto, Canada M5S 2S2
Toxicology 209:113-8. 2005..Reactive metabolites may also act as a danger signal. The models can also be used to test the role of reactive species in the mechanism of hypersensitivity reactions... - Current trends in drug-induced autoimmunityJack Uetrecht
Faculty of Pharmacy, University of Toronto, 19 Russell St, Toronto, Canada M5S 2S2
Autoimmun Rev 4:309-14. 2005..However, there is no clear evidence to suggest that there is one simple mechanism by which drugs induce autoimmunity, and it is likely that several mechanisms may be involved and they may be different for different drugs... - Role of animal models in the study of drug-induced hypersensitivity reactionsJack Uetrecht
Department of Pharmacology, Clinical Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada
AAPS J 7:E914-21. 2005..More animal models are needed to study the range of mechanisms involved in DHRs; without them, progress in understanding such reactions is likely to be slow... - Idiosyncratic drug reactions: current understandingJack Uetrecht
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 2S2, Canada
Annu Rev Pharmacol Toxicol 47:513-39. 2007..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... - Evaluation of which reactive metabolite, if any, is responsible for a specific idiosyncratic reactionJack Uetrecht
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada
Drug Metab Rev 38:745-53. 2006.... - Idiosyncratic drug reactions: past, present, and futureJack Uetrecht
Leslie Dan Facultyof Pharmacy, University of Toronto, Toronto, Canada
Chem Res Toxicol 21:84-92. 2008..However, IDRs are an important cause of patient morbidity and mortality and markedly increase the uncertainty of drug development; therefore, continued basic research in this area is essential... - Immune-mediated adverse drug reactionsJack Uetrecht
Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto M5S 3M2, Canada
Chem Res Toxicol 22:24-34. 2009..Although testing these hypotheses represents a difficult challenge, the importance of these adverse reactions makes it a high priority... - Involvement of the immune system in idiosyncratic drug reactionsXiaochu Zhang
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada
Drug Metab Pharmacokinet 26:47-59. 2011..The observation that IDRs can vary widely among different drugs and different patients is most easily explained by an immune mechanism in which the target of the immune response is different... - Prediction of a new drug's potential to cause idiosyncratic reactionsJ Uetrecht
Faculties of Pharmacy and Medicine, University of Toronto, 19 Russell Street, Toronto, M5S 2S2, Canada
Curr Opin Drug Discov Devel 4:55-9. 2001..Ultimately, it is likely that a much better understanding of the mechanisms involved in such reactions will be required to make real progress... - Screening for the potential of a drug candidate to cause idiosyncratic drug reactionsJack Uetrecht
Faculty of Pharmacy, University of Toronto, 19 Russell St, Toronto, Canada M5S 2S2
Drug Discov Today 8:832-7. 2003..This review highlights the current mechanistic hypotheses of IDRs and discusses future directions in the development of better predictive tests... - N-oxidation of drugs associated with idiosyncratic drug reactionsJack Uetrecht
Faculty of Pharmacy, University of Toronto, Canada
Drug Metab Rev 34:651-65. 2002.... - Predicting drug-induced agranulocytosis: characterizing neutrophil-generated metabolites of a model compound, DMP 406, and assessing the relevance of an in vitro apoptosis assay for identifying drugs that may cause agranulocytosisS Iverson
Faculty of Pharmacy, University of Toronto, 19 Russell Street, Toronto, Canada M5S 2S2
Chem Biol Interact 142:175-99. 2002..This is not a surprising result given that different drugs may induce agranulocytosis by different mechanisms... - Factors that modify penicillamine-induced autoimmunity in Brown Norway rats: failure of the Th1/Th2 paradigmE Sayeh
Faculty of Pharmacy, University of Toronto, 19 Russell Street, Toronto, Canada M5S 2S2
Toxicology 163:195-211. 2001..These results, although dramatic, suggest that the effects of these agents were not mediated by their effects on Th1/Th2 balance, but rather by some other mechanism... - Is it possible to more accurately predict which drug candidates will cause idiosyncratic drug reactions?J P Uetrecht
Faculty of Pharmacy, University of Toronto, Canada
Curr Drug Metab 1:133-41. 2000.... - Identification of a reactive metabolite of terbinafine: insights into terbinafine-induced hepatotoxicityS L Iverson
Faculties of Pharmacy, University of Toronto, Toronto, Ontario, Canada
Chem Res Toxicol 14:175-81. 2001..Alternatively, it could modify canalicular proteins and lead to an immune-mediated reaction causing cholestatic dysfunction... - Bioactivation of clozapine by murine cardiac tissue in vivo and in vitroDominic P Williams
Department of Pharmacology and Therapeutics, The University of Liverpool, Liverpool, United Kingdom
Chem Res Toxicol 16:1359-64. 2003..5 +/- 0.06%, respectively. These data indicate that clozapine undergoes bioactivation in the heart to a chemically reactive nitrenium metabolite that may be important in the pathogenesis of myocarditis and cardiomyopathy observed in man...