Therapeutic Drug Monitoring

Amitava Dasgupta received his Ph. D in chemistry from Stanford University and completed his fellowship training in Clinical Chemistry from the Department of Laboratory Medicine at the University of Washington School of Medicine at Seattle. He is board certified in both Toxicology and Clinical Chemistry by the American Board of Clinical Chemistry. Currently, he is a tenured Full Professor of Pathology and Laboratory Medicine at the University of Kansas Medical Center and Director of Clinical Laboratories at the University of Kansas Hospital. Prior to this appointment he was a tenured Professor of Pathology and Laboratory Medicine at the University of Texas McGovern medical School from February 1998 to April 2022. He has 252 papers to his credit. He is in the editorial board of four journals including Therapeutic Drug Monitoring, Clinica Chimica Acta, Archives of Pathology and Laboratory Medicine, and Journal of Clinical Laboratory Analysis.

Contents Contributors Preface 1. Introduction to therapeutic drug monitoring: Frequently and less frequently monitored drugs Amitava Dasgupta 1. Introduction 2. Drugs that require therapeutic drug monitoring 3. Benefits of therapeutic drug monitoring 4. Pathophysiological conditions and other factors that affect drug concentrations 5. Therapeutic drug monitoring of various drug class 6. Conclusions References 2. Effects of preanalytical variables in therapeutic drug monitoring Janetta Bryksin and Heather Stieglitz 1. Introduction 2. Lab-related variables 3. Patient-specific variables 4. Conclusions References Further reading 3. Analytical techniques used in therapeutic drug monitoring Michael C. Milone 1. Introduction 2. A general classification of analytical methods 3. Understanding and minimizing measurement uncertainty in the clinical laboratory 4. Immunoassays 5. Gas and liquid chromatography 6. Mass spectrometry and LC-MS/MS application to TDM 7. Conclusions References 4. Therapeutic drug monitoring using alternative specimens: Saliva and dried blood spot Kenichi Tamama 1. Introduction 2. Free drug hypothesis 3. Remote sampling for TDM 4. Oral fluid (saliva) 5. Saliva for TDM 6. Saliva collection 7. Factors affecting the distribution of the analytes in DBS 8. DBS with the precise volume deposition 9. Dried plasma spot 10. DBS for TDM 11. Specimen collection for DBS (and VAMS) 12. Laboratory analysis of saliva and dried blood spot 13. Conclusions References 5. Clinical utility of free-drug monitoring Florin Marcel Musteata 1. Introduction 2. Free concentrations versus total concentrations 3. Applications and methods for monitoring free drug concentrations 4. Alternative methods 5. Conclusions References 6. Therapeutic drug monitoring of classical and newer anticonvulsants Matthew Luke 1. Introduction 2. Pathophysiology of epilepsy 3. Antiepileptic drug monitoring 4. Indications for measuring a drug level 5. Therapeutic drug monitoring of classical AEDs 6. Newer anticonvulsants 7. Therapeutic monitoring of brivaracetam 8. Therapeutic monitoring of cannabidiol 9. Therapeutic monitoring of cenobamate 10. Therapeutic monitoring of clobazam 11. Therapeutic drug monitoring of eslicarbazepine acetate 12. Therapeutic drug monitoring of felbamate 13. Monitoring of fenfluramine 14. Monitoring of gabapentin 15. Therapeutic drug monitoring of lacosamide 16. Therapeutic drug monitoring of lamotrigine 17. Therapeutic drug monitoring of levetiracetam 18. Therapeutic drug monitoring of oxcarbazepine 19. Therapeutic drug monitoring of perampanel 20. Therapeutic drug monitoring of pregabalin 21. Therapeutic drug monitoring of rufinamide 22. Therapeutic drug monitoring of stiripentol 23. Therapeutic drug monitoring of tiagabine 24. Therapeutic drug monitoring of topiramate 25. Therapeutic drug monitoring of vigabatrin 26. Therapeutic drug monitoring of zonisamide 27. Analytical methods for monitoring of AEDs 28. Conclusion References 7. Challenges in therapeutic drug monitoring of digoxin and other antiarrhythmic drugs Amitava Dasgupta 1. Introduction 2. Challenges in therapeutic drug monitoring of digoxin 3. Therapeutic drug monitoring of other antiarrhythmic drugs 4. Chromatographic methods for determining multiple antiarrhythmic drugs simultaneously 5. Conclusions References 8. Guidelines for monitoring vancomycin, aminoglycosides, and other antibiotics Amy L. Pyle-Eilola 1. Introduction 2. Vancomycin 3. Aminoglycosides 4. Therapeutic drug monitoring of beta-lactam antibiotics 5. Therapeutic drug monitoring sulfonamides and trimethoprim 6. Therapeutic drug monitoring of chloramphenicol and tetracycline 7. Therapeutic drug monitoring of quinolones 8. Therapeutic drug monitoring of macrolides 9. Therapeutic drug monitoring of antimycobacterial agents 10. Conclusions References 9. Challenges in therapeutic drug monitoring of classical tricyclic and newer antidepressants: analytical and pharmacogenetics considerations Uttam Garg and Angela Ferguson 1. Introduction 2. Tricyclic antidepressants 3. Newer antidepressants 4. Pharmacogenetic considerations in TDM of antidepressants 5. Conclusions References 10. Antiretroviral drug therapeutic drug monitoring for the management of human immunodeficiency infection Patrick D. DeArmond and Dustin R. Bunch Abbreviations 1. Introduction 2. Role of therapeutic drug monitoring 3. TDM instrumentation and matrices of antiretroviral drugs 4. TDM of antiretroviral drugs by classes 5. Challenges in practical application of TDM in managing patients with HIV 6. Conclusion References 11. Therapeutic drug monitoring of selected antifungal agents Matthew D. Krasowski 1. Introduction 2. Overview of therapeutic drug monitoring of antifungal drugs 3. Analytical methods to support TDM of antifungal drugs 4. Specific antifungal drugs 5. Conclusions References 12. Therapeutic drug monitoring of selected direct oral anticoagulants Emmanuel J. Favaloro and Robert C. Gosselin 1. Introduction 2. DOAC: Pharmacokinetic, pharmacodynamics, clinical indications, and dosing 3. DOAC measurementsdoverview 4. Conclusion References 13. Drug testing in pain management Bridgit O. Crews and Amadeo J. Pesce 1. Introduction 2. Utility and cost of drug testing in pain management 3. Substance abuse and addiction medicine 4. Drug testing approaches 5. Drug testing menu 6. Results reporting 7. Testing frequency 8. Specimen types and alternative specimens 9. Specimen collection and testing workflow 10. Analytical approaches 11. Specific analytes and interpretation 12. Stimulants 13. Novel psychoactive substances 14. Pharmacogenomics 15. Conclusions References Further reading 14. An introduction to personalized medicine Joshua Bornhorst 1. Introduction 2. Overview of classical sequence variation profiling techniques 3. Recent molecular profiling technologies 4. Select example biomarkers in pharmacogenomics 5. Translational approaches associated with pharmacogenomics and personalized medicine 6. Conclusions References Further reading 15. Genomic technology advances and the promise for precision medicine Jacopo Umberto Verga, Adam Lloyd, Arthur Sarron, and Gary Hardiman 1. Introduction 2. DNA microarrays 3. Sequencing technologies 4. Pharmacogenetic testing and healthcare 5. Systems medicine 6. Disease diagnosis 7. Drug discovery 8. Precision medicine 9. Challenges in machine learning for systems medicine 10. Conclusion 11. Future prospects References 16. Pharmacogenomics and warfarin therapy Jennifer Martin 1. Introduction 2. The potential of pharmacogenetics for warfarin 3. Pharmacology 4. Nongenetic factors affecting warfarin dosing 5. Clinical relevance 6. Cost-effectiveness of pharmacogenomics testing in warfarin therapy 7. Conclusion References 17. Drug hypersensitivity linked to genetic variations of human leukocyte antigen Debleena Guin and Ritushree Kukreti 1. Introduction 2. HLA: Molecular structure, genomic organization, polymorphism, and nomenclature 3. Repositories related to HLA alleles and associated ADRs 4. HLA alleles and their association with drug-induced ADRs 5. Steven Johns syndrome/toxic epidermal necrolysis (SJS/TEN) 6. Morbilliform drug eruption 7. Drug reaction with eosinophilia and systemic symptoms DRESS 8. Drug-induced liver injury 9. Clinical recommendations for HLA genotyping 10. Conclusions Acknowledgment References 18. Therapeutic drug monitoring of selected anticancer drugs: pharmacogenomics issues Michael C. Milone 1. Introduction 2. Traditional therapeutic drug monitoring for anticancer drugs 3. Newer approaches to personalized dosing and treatment with anticancer agents: pharmacogenetics 4. Pharmacogenetic considerations for specific anti-cancer agents 5. Conclusions References 19. Consequences of differences in bio-analytical assays for the precision monitoring of immunosuppressive drugs Serge Cremers and Alex Lyashchenko 1. Introduction 2. Immunosuppressive drugs and their metabolites 3. Sample matrix 4. Various analytical techniques for measuring immunosuppressants 5. Stability 6. Proficiency testing and comparison studies 7. Interassay differencesdare they relevant? 8. Conclusions References 20. Donor-derived cell-free DNA as a marker of graft injury after solid organ transplantation Michael Oellerich, Klemens Budde, Kirsten Bornemann-Kolatzki, Karen Sherwood, Bilgin Osmanodja, Michael Melter, Julia Beck, Ekkehard Schütz, Paul Keown, and Philip D. Walson 1. Introduction 2. Causes of chronic allograft dysfunction 3. Need for biomarkers 4. Value of conventional TDM 5. Biomarkers for immune monitoring as supplement to TDM 6. Molecular methods: Biopsy and cellular approaches 7. Conclusions References 21. Pharmacodynamic monitoring as an integral part of therapeutic drug monitoring Loralie J. Langman and Paul J. Jannetto 1. Introduction 2. Drug concentrations 3. Pharmacodynamic monitoring 4. Physiological biomarkers 5. Laboratory biomarkers 6. Drug-specific and nonspecific PD biomarkers 7. Summary References 22. Role of therapeutic drug monitoring to identify clinically significant drug-herbal supplement interaction Sergei Likhodii, Alex C. Chin, and Leland B. Baskin 1. Introduction 2. Herbedrug interaction mechanisms 3. Impact of herb supplements and herbedrug interactions in clinical practice 4. Contamination of herbal supplements 5. Analytical interferences caused by some herbal supplements 6. Conclusions References Index