Personalized Immunosuppression in Transplantation,
Edition 1 Role of Biomarker Monitoring and Therapeutic Drug Monitoring
Edited by Michael Oellerich, MD, Hon MD, FACB, FAMM, FFPath (RCPI), FRCPath and Amitava Dasgupta

Publication Date: 03 Sep 2015
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Description

Personalized Immunosuppression in Transplantation: Role of Biomarker Monitoring and Therapeutic Drug Monitoring provides coverage of the various approaches to monitoring immunosuppressants in transplant patients, including the most recently developed biomarker monitoring methods, pharmacogenomics approaches, and traditional therapeutic drug monitoring.

The book is written for pathologists, toxicologists, and transplant surgeons who are involved in the management of transplant patients, offering them in-depth coverage of the management of immunosuppressant therapy in transplant patients with the goal of maximum benefit from drug therapy and minimal risk of drug toxicity.

This book also provides practical guidelines for managing immunosuppressant therapy, including the therapeutic ranges of various immunosuppressants, the pitfalls of methodologies used for determination of these immunosuppressants in whole blood or plasma, appropriate pharmacogenomics testing for organ transplant recipients, and when biomarker monitoring could be helpful.

Key Features

  • Focuses on the personalized management of immunosuppression therapy in individual transplant patients
  • Presents information that applies to many areas, including gmass spectrometry, assay design, assay validation, clinical chemistry, and clinical pathology
  • Provides practical guidelines for the initial selection and subsequent modifications of immunosuppression therapy in individual transplant patients
  • Reviews the latest research in biomarker monitoring in personalizing immunosuppressant therapy, including potential new markers not currently used, but with great potential for future use
  • Explains how monitoring graft-derived, circulating, cell free DNA has shown promise in the early detection of transplant injury in liquid biopsy
About the author
Edited by Michael Oellerich, MD, Hon MD, FACB, FAMM, FFPath (RCPI), FRCPath, Lower Saxony Distinguished Professor of Clinical Chemistry, George-August University, University Medical Center Göttingen, Department of Clinical Pharmacology, Göttingen, Germany and Amitava Dasgupta, Professor, Pathology and Laboratory Medicine, McGovern Medical School, The University of Texas, Houston, TX, USA
Table of Contents
  • Preface
  • List of Contributors
  • Chapter 1. Overview of the pharmacology and toxicology of immunosuppressant agents that require therapeutic drug monitoring
    • 1.1 Introduction
    • 1.2 Calcineurin Inhibitors
    • 1.3 Antimetabolite Drug
    • 1.4 Mammalian Target of Rapamycin Inhibitors
    • 1.5 Conclusions
    • References
  • Chapter 2. Limitations of immunoassays used for therapeutic drug monitoring of immunosuppressants
    • 2.1 Introduction
    • 2.2 Methods for Therapeutic Drug Monitoring of Immunosuppressants
    • 2.3 Cyclosporine Monitoring: Trough or C2 Monitoring?
    • 2.4 Limitations of Immunoassays Used for Cyclosporine Monitoring
    • 2.5 Limitations of Immunoassays Used for Tacrolimus Monitoring
    • 2.6 Limitations of Immunoassays Used for Sirolimus Monitoring
    • 2.7 Limitations of Immunoassays Used for Everolimus Monitoring
    • 2.8 Limitations of Immunoassays Used for Mycophenolic Acid Monitoring
    • 2.9 Conclusions
    • References
  • Chapter 3. Application of liquid chromatography combined with mass spectrometry or tandem mass spectrometry for therapeutic drug monitoring of immunosuppressants
    • 3.1 Introduction
    • 3.2 Evolution of Non-Immunoassay Methods for Immunosuppressants
    • 3.3 LC–MS/MS Methods for Analysis of Immunosuppressants
    • 3.4 Limitation of Mass Spectrometric Methods
    • 3.5 Turnaround Time
    • 3.6 Conclusions
    • References
  • Chapter 4. Monitoring free mycophenolic acid concentration: Is there any clinical advantage?
    • 4.1 Introduction
    • 4.2 Monitoring Free Drug Concentration
    • 4.3 Monitoring Free (Unbound) Fraction of Cyclosporine
    • 4.4 Monitoring Free (Unbound) Fraction of Tacrolimus and Sirolimus
    • 4.5 Mycophenolic Acid: A Brief Introduction
    • 4.6 Rationale for Therapeutic Drug Monitoring of Mycophenolic Acid
    • 4.7 Conclusion
    • References
  • Chapter 5. Pharmacogenomics aspect of immunosuppressant therapy
    • 5.1 Introduction
    • 5.2 Individual Genes
    • 5.3 Conclusions
    • References
  • Chapter 6. Biomarker monitoring in immunosuppressant therapy: An overview
    • 6.1 Introduction
    • 6.2 Current Immunosuppressive Agents and Their Effects on Immune Responsiveness
    • 6.3 Biomarkers to Guide Immunosuppressant Therapy
    • 6.4 Calcineurin Phosphate
    • 6.5 Nuclear Factor of Activated T Lymphocytes Regulated Gene Expression
    • 6.6 Inosine Monophosphate Dehydrogenase
    • 6.7 Phosphorylation of mTOR Downstream Effectors
    • 6.8 Pharmacogenetic Biomarkers
    • 6.9 Biomarkers Nonspecific for Single Drug Action
    • 6.10 Conclusions
    • References
  • Chapter 7. Graft-derived cell-free DNA as a marker of graft integrity after transplantation
    • 7.1 Introduction
    • 7.2 Causes of Chronic Allograft Dysfunction
    • 7.3 Need for Biomarkers
    • 7.4 Value of Conventional TDM
    • 7.5 Biomarkers for Immune Monitoring as Supplement to TDM
    • 7.6 Molecular Methods: Biopsy and Cellular Approaches
    • 7.7 Conclusions
    • Acknowledgments
    • References
  • Chapter 8. Biomarkers of tolerance in kidney transplantation
    • 8.1 Introduction
    • 8.2 Definition of the Clinical Status of Operational Tolerance
    • 8.3 Technical Considerations on the Biodetection of Tolerance
    • 8.4 A B-Cell Signature Predominates in Blood from Tolerant Recipients
    • 8.5 An Unsuspected Role for B Cell in Operational Tolerance
    • 8.6 Potential Applications of the Biomarkers and the Future for Tolerance Research
    • 8.7 Conclusions
    • References
  • Chapter 9. Intracellular concentrations of immunosuppressants
    • 9.1 Introduction
    • 9.2 Measuring Intracellular Concentrations of Immunosuppressants
    • 9.3 Immunosuppressant Drug Concentrations in PBMCs/Lymphocytes
    • 9.4 Drug Transport Across Lymphocyte Cell Membranes: The Role of P-Glycoprotein
    • 9.5 Considerations Regarding Intracellular Drug Monitoring
    • 9.6 Conclusions
    • References
  • Chapter 10. Markers of lymphocyte activation and proliferation
    • 10.1 Introduction
    • 10.2 Lymphocyte Proliferation and Activation in Allograft Rejection
    • 10.3 Effect of Immunosuppressants on Lymphocyte Proliferation and Activation
    • 10.4 Conclusions
    • References
  • Chapter 11. Monitoring calcineurin inhibitors response based on NFAT-regulated gene expression
    • 11.1 Introduction
    • 11.2 Mechanism of Action of CNIs
    • 11.3 Strategies for Pharmacodynamic Monitoring of CNIs
    • 11.4 Measurement of NFAT-Regulated Gene Expression
    • 11.5 Molecular Response to CNI Exposure
    • 11.6 CNI Pharmacodynamics and Clinical Outcome
    • 11.7 Perspectives
    • 11.8 Conclusions
    • References
  • Index
Book details
ISBN: 9780128008850
Page Count: 316
Retail Price : £68.99
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  • Yao, Genomic Biomarkers for Pharmaceutical Development, AP, 9780123973368, Aug 2013, 192 pp., $99.95
Audience

Pathologists, clinical chemists, toxicologists, and transplant surgeons who are involved in the routine care of transplant patients; transplant nephrologists, gastroenterologists, cardiologists, pulmonary physicians and fellows in transplantation program and supervisors of toxicology or immunosuppressant monitoring laboratories.