Therapeutic Drug Monitoring

Dedication

Preface

Contributors

Chapter 1. Introduction to Therapeutic Drug Monitoring: Frequently and Less Frequently Monitored Drugs

Introduction

Drugs that Require Therapeutic Drug Monitoring

Benefits of Therapeutic Drug Monitoring

Pathophysiological Conditions and other Factors that Affect Drug Concentrations

Therapeutic Drug Monitoring of Various Drug Classes

Conclusions

References

Chapter 2. Effects of Pre-analytical Variables in Therapeutic Drug Monitoring

Introduction

Specimen Type

Factors that Affect Therapeutic Drug Monitoring Results

Protein Binding Alteration: In Vivo and In Vitro

Specimen Collection Site

Volume of Specimen Collected

Glass versus Plastic Tubes for Collection of Blood

Serum versus Plasma Specimen for Therapeutic Drug Monitoring

Suitability of Serum Separator Collection Tubes for Specimen Collection for Drug Monitoring

Sample Preparation Steps

Conclusions

References

Chapter 3. Analytical Techniques used in Therapeutic Drug Monitoring

Introduction

A General Classification of Analytical Methods

Understanding and Minimizing Measurement Uncertainty in the Clinical Laboratory

Immunoassays

Gas and Liquid Chromatography

Mass Spectrometry and LC-MS/MS Application to TDM

Conclusions

References

Chapter 4. Clinical Utility of Free Drug Monitoring

Introduction

Free Concentrations versus Total Concentrations

Pharmacokinetic Consequences of Drug–Protein Binding

Monitoring Free Concentrations of Classical Anti-Epileptics

Monitoring Free Concentrations of Antibiotics, Antimalarials and Antiretrovirals

Monitoring Free Concentrations of Immunosuppressants

Monitoring Free Concentrations of Other Drugs

Applications and Methods for Monitoring Free Drug Concentrations

Alternative Methods

Conclusions

References

Chapter 5. Current Practice of Therapeutic Drug Monitoring: Dose Adjustment of Drugs using Pharmacokinetic Models

Introduction

Bayesian Estimation

Examples of Clinical Transferability

Conclusion

References

Chapter 6. An Introduction to Personalized Medicine

Introduction

Overview of Classical Sequence Variation Profiling Techniques

Recent Molecular Profiling Technologies

Select Biomarkers in Pharmacogenomics

Translational Approaches Associated with Pharmacogenomics and Personalized Medicine

Conclusions

References

Chapter 7. Application of Ultra-High Throughput Sequencing and Microarray Technologies in Pharmacogenomics Testing

Introduction

DNA Microarray

Pharmacogenetic Testing and Healthcare

DNA Microarray Platforms

Microarrays and Genotype

Microarrays in Clinical Diagnosis

Sequencing Technologies – The First Generation

Sequencing Technologies – Next Generation

Exon Capture and Oligonucleotide-Based Genomic Selection

Microarray Technology versus Deep Sequencing

Sequencing and Implications for Pharmacogenomics Testing

Conclusions

References

Chapter 8. Pharmacogenomics and Warfarin Therapy

Introduction

The Potential of Pharmacogenetics for Warfarin

Pharmacology

Non-Genetic Factors Affecting Warfarin Dosing

Clinical Relevance

Cost-Effectiveness of Pharmacogenomics Testing in Warfarin Therapy

New Medications to Replace Warfarin

Conclusions

References

Chapter 9. Applications of Pharmacokinetic and Pharmacodynamic Principles to Optimize Drug Dosage Selection: Example of Antibiotic Therapy Management

Introduction

Pharmacokinetics and Pharmacodynamics

Applied Pharmacokinetic/Pharmacodynamic Modeling

Conclusions

References

Chapter 10. Guidelines for the Monitoring of Vancomycin, Aminoglycosides and Certain Antibiotics

Introduction

Vancomycin: Overview

Aminoglycosides: Overview

Therapeutic Drug Monitoring of Beta-Lactam Antibiotics

Therapeutic Drug Monitoring of Sulfonamides and Trimethoprim

Therapeutic Drug Monitoring of Chloramphenicol and Tetracycline

Therapeutic Drug Monitoring of Quinolones

Therapeutic Drug Monitoring of Macrolides

Therapeutic Drug Monitoring of Antimycobacterial Agents

Conclusions

References

Chapter 11. Challenges in Therapeutic Drug Monitoring of Digoxin and Other Anti-Arrhythmic Drugs

Introduction

Challenges in Therapeutic Drug Monitoring of Digoxin

Therapeutic Drug Monitoring of Other Anti-Arrhythmic Drugs

Challenges in Monitoring Class IV Anti-Arrhythmic Drugs

Chromatographic Methods for Determining Multiple Anti-Arrhythmic Drugs Simultaneously

Conclusions

References

Chapter 12. Therapeutic Drug Monitoring of Classical and Newer Anticonvulsants

Introduction

Pathophysiology of Epilepsy

Anti-Epileptic Drug Monitoring

Indications for Measuring a Drug Level

Therapeutic Drug Monitoring of Classical AEDs

Newer Anticonvulsants

Therapeutic Drug Monitoring of Eslicarbazepine Acetate

Therapeutic Drug Monitoring of Felbamate

Monitoring of Gabapentin

Therapeutic Drug Monitoring of Lacosamide

Therapeutic Drug Monitoring of Lamotrigine

Therapeutic Drug Monitoring of Levetiracetam

Therapeutic Drug Monitoring of Oxcarbazepine

Therapeutic Drug Monitoring of Pregabalin

Therapeutic Drug Monitoring of Rufinamide

Therapeutic Drug Monitoring of Stiripentol

Therapeutic Drug Monitoring of Tiagabine

Therapeutic Drug Monitoring of Topiramate

Therapeutic Drug Monitoring of Vigabatrin

Therapeutic Drug Monitoring of Zonisamide

Analytical Methods for Monitoring of AEDs

Conclusion

References

Chapter 13. Challenges in Therapeutic Drug Monitoring of Classical Tricyclic and Newer Antidepressants: Analytical and Pharmacogenetics Considerations

Introduction

Tricyclic Antidepressants

Newer Antidepressants

Pharmacogenetics Considerations in TDM of Antidepressants

Conclusions

References

Chapter 14. Therapeutic Drug Monitoring of Selected Anticancer Drugs: Pharmacogenomics Issues

Introduction

Traditional Therapeutic Drug Monitoring for Anticancer Drugs

Newer Approaches to Personalized Dosing and Treatment with Anticancer Agents: Pharmacogenetics

Pharmacogenetic Considerations for Specific Anticancer Agents

Anti-EGFR Tyrosine Kinase Inhibitors

Conclusions

References

Chapter 15. Immunosuppressive Drug Monitoring: Limitations of Immunoassays and the Application of Liquid Chromatography Mass Spectrometry

Introduction

Application of Immunoassays and LC-MS to Immunosuppressive Drug Monitoring

Therapeutic Drug Monitoring of Calcineurin Inhibitors (Cyclosporine and Tacrolimus)

Therapeutic Drug Monitoring of Mammalian Target of Rapamycin (MTOR) Inhibitors (Sirolimus and Everolimus)

Therapeutic Drug Monitoring of Mycophenolic Acid

Conclusions

References

Chapter 16. Biomarkers: The Link between Therapeutic Drug Monitoring and Pharmacodynamics of Immunosuppressants

Introduction

Specific Pharmacodynamic Markers

Global Markers of Response to Immunosuppressants

Biomarker Signatures Related to Tolerance

Conclusions

References

Chapter 17. Therapeutic Drug Monitoring of Antiretroviral Drugs in the Management of Human Immunodeficiency Virus Infection

Introduction

Therapeutic Targets of Therapeutic Drug Monitoring (TDM) in HIV-infected Patients

Current Approach to TDM in the Management of Therapy in HIV-infected Patients

Current Methodologies in TDM of Antiretroviral Drugs

TDM of Antiretroviral Drugs by Classes

Challenges in Practical Application of TDM in Managing Patients with HIV

Conclusion

References

Chapter 18. Drug Testing in Pain Management

Introduction

Use of Opioids in Pain Management

Analytical Methods for Drug Testing

Specimen Tampering

Metabolism of Opioid Analgesics

Challenges in Drug Testing in Pain Management

Conclusions

References

Chapter 19. Effect of Herbal Supplement–Drug Interactions on Therapeutic Drug Monitoring

Introduction

Herbal Supplements and Pharmacokinetics

Pharmacokinetic Interactions Involving Herbal Supplements

Contamination of Herbal Supplements

Analytical Interferences Caused by Some Herbal Supplements

Conclusions

References

Index