Abstract
Thiopurines are widely used in the treatment of inflammatory bowel disease (IBD). However, in clinical practice azathioprine (AZA) or 6-mercaptopurine (6-MP) are not effective in one-third of patients and up to one-fifth of patients discontinue thiopurine therapy due to adverse reactions. The observed interindividual differences in therapeutic response and toxicity to thiopurines are explained to a large extent by the variable formation of active metabolites, which is at least partly caused by genetic polymorphisms of the genes encoding crucial enzymes in thiopurine metabolism. In this in-depth review we discuss the genetic polymorphisms of genes encoding for glutathione S-tranferases, xanthine oxidase, thiopurine S-methyltransferase, inosine triphosphate pyrophosphatase, hypoxanthine phosphoribosyltransferase, inosine monophosphate dehydrogenase and multidrug resistance proteins. Pharmacogenetic knowledge in this field has increased dramatically and is still rapidly increasing, but the translation into practical guidelines with tailored advices will cost much effort in the near future.
Current Pharmaceutical Design
Title: Pharmacogenetics of Thiopurines in Inflammatory Bowel Disease
Volume: 16 Issue: 2
Author(s): L. J.J. Derijks and D. R. Wong
Affiliation:
Abstract: Thiopurines are widely used in the treatment of inflammatory bowel disease (IBD). However, in clinical practice azathioprine (AZA) or 6-mercaptopurine (6-MP) are not effective in one-third of patients and up to one-fifth of patients discontinue thiopurine therapy due to adverse reactions. The observed interindividual differences in therapeutic response and toxicity to thiopurines are explained to a large extent by the variable formation of active metabolites, which is at least partly caused by genetic polymorphisms of the genes encoding crucial enzymes in thiopurine metabolism. In this in-depth review we discuss the genetic polymorphisms of genes encoding for glutathione S-tranferases, xanthine oxidase, thiopurine S-methyltransferase, inosine triphosphate pyrophosphatase, hypoxanthine phosphoribosyltransferase, inosine monophosphate dehydrogenase and multidrug resistance proteins. Pharmacogenetic knowledge in this field has increased dramatically and is still rapidly increasing, but the translation into practical guidelines with tailored advices will cost much effort in the near future.
Export Options
About this article
Cite this article as:
Derijks J.J. L. and Wong R. D., Pharmacogenetics of Thiopurines in Inflammatory Bowel Disease, Current Pharmaceutical Design 2010; 16 (2) . https://dx.doi.org/10.2174/138161210790112773
DOI https://dx.doi.org/10.2174/138161210790112773 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Limiting Functional Deficiency Following Stroke: Exploiting Different Stem Cell Reservoirs
Current Neuropharmacology Nanoparticles for Tumor Targeted Therapies and Their Pharmacokinetics
Current Drug Metabolism Edelfosine in Membrane Environment - the Langmuir Monolayer Studies
Anti-Cancer Agents in Medicinal Chemistry Targeting Blood Vessels for the Treatment of Non-Small Cell Lung Cancer
Current Cancer Drug Targets Predictive Markers for Haematological Toxicity of Pemetrexed
Current Drug Targets Metallothioneins and Cancer
Current Protein & Peptide Science Towards Liver-Directed Gene Therapy for Crigler-Najjar Syndrome
Current Gene Therapy Advances in the Management of Malignant Hemopathies: The Role of Statins
Recent Patents on DNA & Gene Sequences Mitochondria in Cancer Stem Cells: A Target for Therapy
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued) Animal Models of Atherosclerosis Progression: Current Concepts
Current Drug Targets - Cardiovascular & Hematological Disorders Management of Inflammation by Natural Polyphenols: A Comprehensive Mechanistic Update
Current Medicinal Chemistry B7-H3-targeted Radioimmunotherapy of Human Cancer
Current Medicinal Chemistry Some Implications of Receptor Kinase Signaling Pathway for Development of Multitargeted Kinase Inhibitors
Current Radiopharmaceuticals Stable Expression of the Sodium/Iodide Symporter (NIS) for anti-Cancer Gene Therapy of Glioma Cells Using a Third Generation Self-Inactivating Lentiviral Vector System in Combination with 211At
Current Radiopharmaceuticals Targeted Anti-leukemic Therapy as Disease-stabilizing Treatment for Acute Myeloid Leukemia Relapse after Allogeneic Stem Cell Transplantation: Will it be Possible to Combine these Strategies with Retransplantation or Donor Lymphocyte Infusions?
Current Cancer Drug Targets Induced Pluripotent Stem Cells (iPSCs) Derived from Different Cell Sources and their Potential for Regenerative and Personalized Medicine
Current Molecular Medicine Resveratrol and Neurodegenerative Diseases: Activation of SIRT1 as the Potential Pathway towards Neuroprotection
Current Neurovascular Research The Use of the Zebrafish Model to Aid in Drug Discovery and Target Validation
Current Topics in Medicinal Chemistry A Brief Review of the Essential Role of Nanovehicles for Improving the Therapeutic Efficacy of Pharmacological Agents Against Tumours
Current Drug Delivery miRNAs in Cancer Prevention and Treatment and as Molecular Targets for Natural Product Anticancer Agents
Current Cancer Drug Targets