• KOL
    • Liver Injury
    • Jack Paul Uetrecht
    • Jack Paul Uetrecht: Influence Statistics

      Jack Paul Uetrecht

      Jack Paul Uetrecht

      Show email address

      Pharmaceutical Sciences, University of Toronto, 144 College Street, Toronto, Ontario, M5S 3M2, Canada | Faculty of Pharmaceutical Sciences, University of Toronto, Toronto, ON, ...

      Is this your profile? manage_accounts Claim your profile content_copy Copy URL code Embed Link to your profile

      Jack Paul Uetrecht:Expert Impact

      Concepts for whichJack Paul Uetrechthas direct influence:Liver injury,Covalent binding,Reactive metabolites,Idiosyncratic drug reactions,Reactive metabolite,Skin rash,Brown norway,Danger hypothesis.

      Jack Paul Uetrecht:KOL impact

      Concepts related to the work of other authors for whichfor which Jack Paul Uetrecht has influence:Liver injury,Reactive metabolites,Cytochrome p450,Drug metabolism,Oxidative stress,Covalent binding,Hypersensitivity reactions.

      KOL Resume for Jack Paul Uetrecht

      Year
      2022

      Pharmaceutical Sciences, University of Toronto, 144 College Street, Toronto, Ontario, M5S 3M2, Canada

      2021

      Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5S 1A8, Canada;,

      Leslie Dan Faculty of Pharmacy, Faculty of Medicine, University of Toronto, Toronto M5S3M2, Canada

      2020

      Department of Pharmaceutical Scinces, Faculty of Pharmacy, University of Toronto, Canada.

      University of Toronto, Toronto, ON, Canada

      2019

      Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada, View further author information

      Faculties of Pharmacy and Medicine, University of Toronto, Toronto, ON, Canada

      2018

      Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canadahttp://orcid.org/0000-0003-1024-1302View further author information

      Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Ontario, M5S 3H7, Canada

      University of Toronto, Toronto, ON, United States

      2017

      University of Toronto Leslie Dan Faculty of Pharmacy Toronto Ontario Canada

      2016

      University of Toronto Leslie Dan Faculty of Pharmacy, Department of Pharmaceutical Sciences Toronto ON Canada

      2015

      University of Toronto Department of Pharmaceutical Sciences, Faculty of Pharmacy Toronto Ontario Canada

      2014

      Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario, M5S 3M2, Canada

      2013

      Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 1A8

      Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario, Canada, M5S 3M2

      University of Toronto, Toronto, Ontario Canada

      2012

      Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada

      2011

      University of Toronto Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy Toronto Ontario Canada

      2010

      University of Toronto.

      2009

      Department of Pharmaceutical Sciences, University of Toronto, Toronto, Canada

      Faculty of Medicine.

      2008

      Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada, and Department of Exercise and Nutrition Sciences, University at Buffalo, Buffalo, New York

      2007

      Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Ontario, Canada

      2006

      Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 3M2, Canada, Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario N1G 2W1, Canada, and Department of Immunotoxicology, Pharmaceutical Research Institute, Bristol-Myers Squibb Company, East Syracuse, New York

      Pharmacy and Medicine, University of Toronto, Toronto, Canada

      2005

      Faculties of Pharmacy and Medicine, University of Toronto, Toronto, Ontario M5S 2S2, Canada

      2004

      Faculty of Pharmacy, University of Toronto, 19 Russell Street, Toronto, Ont., Canada M5S 2S2

      2003

      Faculty of Pharmacy, University of Toronto, Toronto, Canada

      2002

      Faculty of Medicine, University of Toronto, 19 Russell Street, Toronto, Canada M55 252

      2001

      Faculty of Pharmacy, University of Toronto, 19 Russell Street, Toronto, Canada M5S2S2

      2000

      Department of Pharmacology and Therapeutics, The University of Liverpool, Liverpool, United Kingdom (D.P.W., M.P., D.J.N., B.K.P.); and 2Faculty of Pharmacy, University of Toronto, Ontario, Canada (J.P.U.)

      Division of Drug Safety Clinic, University of Toronto, Toronto, Ontario, Canada

      1999

      Division of Immunology and Division of Toxicology, Medical Institute of Environmental Hygiene at Heinrich Heine University Duesseldorf, Duesseldorf, Germany, Faculty of Pharmacy and Medicine, University of Toronto, Toronto, Ontario, Canada, and Institute of Occupational Physiology at the University of Dortmund, Dortmund, Germany

      1998

      University of Toronto Drug Safety Research Group, Toronto, Ont., Canada

      1997

      Faculties of Pharmacy and Medicine, University of Toronto and Sunnybrook Health Science Centre, 19 Russell St., Toronto, Ontario, Canada M5S 2S2

      Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada, Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada.

      Sign-in to see all concepts, it's free!
      Sample of concepts for which Jack Paul Uetrecht is among the top experts in the world.
      Concept World rank
      carbamazepine metabolized #1
      entacapone liver injury #1
      mechanism hypersensitivityreactions #1
      covalent nvp #1
      contrast drug reactions #1
      idili mediated #1
      halothaneinduced liver toxicity #1
      danger hypothesis smx #1
      risk amodiaquine #1
      idiosyncratic skin #1
      reactive species ability #1
      idrs mechanisms #1
      cells pmvarphi #1
      aromatic amine drug #1
      leukocyte generated #1
      danger hypothesis cbz #1
      hypotheses idili #1
      covalent skin #1
      evidence mechanistic hypotheses #1
      isoniazid food #1
      neutrophils carbamazepine #1
      drugs reactive #1
      hapa formation pmvarphi #1
      4 phn #1
      tolerant rats rats #1
      dhrs animals #1
      amg agranulocytosis #1
      neutrophils olanzapine #1
      idiosyncratic reaction #1
      idili studies #1
      formation reactive metabolite #1
      determinant drugs #1
      noxidation pa #1
      ptu so3 #1
      penicillamine induced #1
      cells amodiaquine #1
      aq neutrophils #1
      induced idili #1
      drug development ways #1
      adverse reactions drug #1
      idiosyncratic nature reactions #1
      amg neutrophils #1
      covalent binding #1
      pd1 mice aq #1
      ly3031207 study #1
      nitrenium ion apoptosis #1
      phn immune #1
      pd1– #1
      lupus chromatography #1
      penicillamine poly #1
      Sign-in to see all concepts, it's free!

      Prominent publications by Jack Paul Uetrecht

      KOL-Index: 13760

      Gilbert's syndrome occurs in 5%-7% of the human population and is caused by an inherited deficiency in the glucuronidation of endogenous bilirubin, resulting in its accumulation and jaundice. The authors of the present study have previously shown that rats with a similar deficiency in bilirubin glucuronidation (Gunn rats) had reduced glucuronidation and enhanced susceptibility to the toxicity of the widely used analgesic, acetaminophen. Acetaminophen is eliminated primarily by ...

      Known for Glucuronidation Acetaminophen | Gilberts Syndrome | Normal Controls | Total Bilirubin | Subjects Gilbert
      KOL-Index: 13445

      Idiosyncratic drug reactions are difficult to study in humans due to their unpredictability. Unfortunately, this characteristic also hinders the development of animal models needed for mechanistic studies. Nevirapine, used to treat human immunodeficiency virus (HIV) infections, results in a severe idiosyncratic skin rash in some patients. We found that nevirapine can also cause a significant rash in some strains of rats. At a dose of 150 mg/kg/day, the incidence in female Sprague-Dawley ...

      Known for Skin Rash | Brown Norway | Idiosyncratic Drug | Animal Model | Nevirapine Rats
      KOL-Index: 13112

      Evidence strongly suggests that many adverse drug reactions, including idiosyncratic drug reactions, involve reactive metabolites. Furthermore, certain functional groups, which are readily oxidized to reactive metabolites, are associated with a high incidence of adverse reactions. Most drugs can probably form reactive metabolites, but a simple comparison of covalent binding in vitro is unlikely to provide an accurate indication of the relative risk of a drug causing an idiosyncratic ...

      Known for Reactive Metabolites | Drug Reactions | Activated Leukocytes | Idiosyncratic Reaction | Neutrophil Precursors
      KOL-Index: 12754

      There is increasing evidence that most idiosyncratic drug-induced liver injury (IDILI) is immune mediated, and in most cases, reactive metabolites appear to be responsible for the induction of this immune response. Reactive metabolites can cause cell damage with the release of damage-associated molecular patterns (DAMPs), which is thought to be involved in immune activation. Presumably, the reason that the liver is a common target of idiosyncratic drug reactions is because it is the ...

      Known for Thp1 Cells | Inflammasome Activation | Reactive Metabolites | Release Damps | Idiosyncratic Liver
      KOL-Index: 12505

      Amodiaquine (AQ) and clozapine (CLZ) are associated with a relatively high incidence of idiosyncratic agranulocytosis, a reaction that is suspected to involve covalent binding of reactive metabolites to neutrophils. Previous studies have shown that both AQ and CLZ are oxidized to reactive intermediates in vitro by activated neutrophils or by the combination of hydrogen peroxide and myeloperoxidase (MPO). Neutrophil activation leads to an oxidative burst with activation of NADPH oxidase ...

      Known for Covalent Binding | Nadph Oxidase | Amodiaquine Aq | Clozapine Clz | Mice Knockout
      KOL-Index: 11617

      Most patients taking drugs associated with idiosyncratic drug reactions tolerate the drug and do not develop adverse reactions. Understanding the mechanism of tolerance to drugs is important as it could provide insight into why some patients develop idiosyncratic reactions and others do not. The Brown Norway rat model of D-penicillamine-induced autoimmunity was used as a model of idiosyncratic drug-induced autoimmunity. Two weeks of low dose (5 mg/day) D-penicillamine pretreatment ...

      Known for Brown Norway | Induced Autoimmunity | Low Dose | Tolerance Immune | Idiosyncratic Reactions
      KOL-Index: 11510

      Amodiaquine (AQ) treatment is associated with a high incidence of idiosyncratic drug-induced liver injury (IDILI) and agranulocytosis. Evidence suggests that AQ-induced IDILI is immune mediated. A significant impediment to mechanistic studies of IDILI is the lack of valid animal models. This study reports the first animal model of IDILI with characteristics similar to mild IDILI in humans. Treatment of female C57BL/6 mice with AQ led to liver injury with delayed onset, which resolved ...

      Known for Induced Liver | Mouse Model | Immune Tolerance | Delayed Onset | Injury Idili
      KOL-Index: 10736

      This review presents a unifying hypothesis that provides a connection between several types of hypersensitivity reactions associated with several types of drugs and explains some of the therapeutic effects (antiinflammatory activity and antithyroid effects) of these same drugs. This hypothesis centers on the oxidation of these drugs to chemically reactive metabolites by peroxidases. The drugs of interest have functional groups that are easily oxidized. The major peroxidase involved in ...

      Known for Drug Metabolism | Reactive Metabolites | Hypersensitivity Reactions | Induced Lupus | Immune Mediated
      KOL-Index: 10654

      Nevirapine (NVP) treatment is associated with serious skin rashes that appear to be immune-mediated. We previously developed a rat model of this skin rash that is immune-mediated and is very similar to the rash in humans. Treatment of rats with the major NVP metabolite, 12-OH-NVP, also caused the rash. Most idiosyncratic drug reactions are caused by reactive metabolites; 12-OH-NVP forms a benzylic sulfate, which was detected in the blood of animals treated with NVP or 12-OH-NVP. This ...

      Known for Covalent Binding | Nvp Skin | Reactive Metabolites | Benzylic Sulfate | Humans Liver
      KOL-Index: 10433

      Our laboratory recently reported what we believe is the first valid animal model of idiosyncratic drug-induced liver injury (IDILI) by treating PD1-/- mice with an anti-CTLA-4 antibody and amodiaquine (AQ). PD1 and CTLA-4 are important immune checkpoint receptors that are involved in inducing immune tolerance. This model was able to produce significant liver injury that looks very similar to the liver injury seen in humans. Although this model was shown to work with AQ, the question ...

      Known for Liver Injury | Drugs Idili | Immune Tolerance | Pd1 Mice | Drug Induced
      KOL-Index: 10406

      The mechanism of idiosyncratic drug-induced liver injury (IDILI) remains poorly understood, to a large degree because of the lack of a valid animal model. Recently, we reported an animal model in which treatment of female C57BL/6 mice with amodiaquine (AQ) resulted in mild liver injury with a delayed onset and resolution despite continued treatment. Such adaptation is a common outcome in the IDILI caused by drugs that can cause liver failure. We had hypothesized that most IDILI is ...

      Known for Liver Injury | Immune Tolerance | Aq Mice | Animal Model | Continued Treatment
      KOL-Index: 10343

      Nevirapine (NVP) treatment is associated with a significant incidence of skin rash in humans, and it also causes a similar immune-mediated skin rash in Brown Norway (BN) rats. We have shown that the sulfate of a major oxidative metabolite, 12-OH-NVP, covalently binds in the skin. The fact that the sulfate metabolite is responsible for covalent binding in the skin does not prove that it is responsible for the rash. We used various inhibitors of sulfation to test whether this reactive ...

      Known for Skin Rash | Covalent Binding | 12 Nvp | Nevirapine Rats | Reactive Sulfate
      KOL-Index: 10193

      Nevirapine (NVP) treatment is associated with a significant incidence of liver injury. We developed an anti-NVP antiserum to determine the presence and pattern of covalent binding of NVP to mouse, rat, and human hepatic tissues. Covalent binding to hepatic microsomes from male C57BL/6 mice and male Brown Norway rats was detected on Western blots; the major protein had a mass of ~55 kDa. Incubation of NVP with rat CYP3A1 and 2C11 or human CYP3A4 also led to covalent binding. Treatment of ...

      Known for Liver Injury | Quinone Methide | Covalent Binding | Mice Nvp | Inbred C57bl Microsomes

      Key People For Liver Injury

      Top KOLs in the world
      #1
      Neil Kaplowitz
      liver injury bile acids gsh transport
      #2
      Hartmut Jaeschke
      liver injury cell death acetaminophen hepatotoxicity
      #3
      William Martens Lee
      acute liver failure chronic hepatitis liver injury
      #4
      Robert John Fontana
      liver injury chronic hepatitis united states
      #5
      David Allen Brenner∥
      liver fibrosis kupffer cells gene expression
      #6
      Paul Brent Watkins
      liver injury cytochrome p450 grapefruit juice

      Pharmaceutical Sciences, University of Toronto, 144 College Street, Toronto, Ontario, M5S 3M2, Canada | Faculty of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada | Department of Pharmacology and Toxicology, University of Toronto,

    Download on the App StoreGet it on Google Play

    Copyright © 2023 Key Opinion Leaders, LLC.