Basics and Clinical Applications of Drug Disposition in Special Populations

Name: Basics and Clinical Applications of Drug Disposition in Special Populations
Brand: Wiley
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Seth Kwabena Amponsah Yashwant V. Pathak(Herausgeber*in)

Wiley (Verlag)

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Erschienen am 26. März 2025

483 Seiten

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Inhalt

Cover
Title Page
Copyright Page
Dedication
Contents
About the Editors
List of Contributors
Foreword
Preface
Chapter 1 Pharmacokinetic Principles and Concepts: An Overview
1.1 Introduction
1.2 Pharmacokinetic Parameters
1.2.1 Absorption
1.2.2 Distribution
1.2.3 Metabolism
1.2.4 Excretion
1.3 Pharmacokinetic Models
1.4 Applications
1.5 Conclusion
References
Chapter 2 Model-Based Pharmacokinetic Approaches
2.1 Introduction
2.1.1 Importance of PK
2.1.2 Overview of Model-Based Approaches
2.2 Basics of Pharmacokinetics
2.2.1 Key Pharmacokinetic Parameters
2.2.1.1 Absorption
2.2.1.2 Key Parameter
2.2.1.3 Distribution
2.2.1.4 Key Parameter
2.2.1.5 Metabolism
2.2.1.6 Key Parameter
2.2.1.7 Excretion
2.2.1.8 Key Parameter
2.2.2 Differences Between Traditional and Model-Based Pharmacokinetic Approaches
2.3 Pharmacokinetic (PK) Models
2.3.1 Introduction
2.3.2 Compartment Modeling
2.3.2.1 One-CompartmentModel
2.3.2.2 Multi-CompartmentModel
2.3.2.3 Two-CompartmentModel
2.3.3 Population PK Model
2.3.4 Physiologically Based PK (PBPK) Model
2.4 Model Development and Validation
2.4.1 Data Requirements for Model Development
2.4.2 Data Requirements for Model Validation
2.4.3 Steps in Model Building (E.g., Model Selection and Parameter Estimation)
2.5 Applications of Model-Based Approaches
2.5.1 Dose Optimization
2.5.2 Predicting Drug Interactions
2.5.3 Drug Tailoring in Special Populations (E.g., Pediatrics, Geriatrics, and Renal Impairment)
2.5.4 Translational PK from Preclinical to Clinical Settings
2.6 Modeling in Special Populations
2.6.1 Challenges and Considerations
2.6.1.1 Challenges in PK Modeling
2.6.1.2 Considerations in PK Modeling
2.7 Software and Tools for PK Modeling
2.7.1 GastroplusT
2.7.2 Berkeley Madonna
2.7.3 MATLAB
2.7.4 PK-Sim®
2.7.5 Simcyp®
2.7.6 Auxiliary PBPK Modeling Software
2.7.6.1 Julia
2.7.6.2 NONMEM
2.7.6.3 Phoenix WinNonlin
2.7.6.4 GraphPad Prism
2.7.6.5 Minitab
2.7.6.6 PlotDigitizer
2.7.6.7 GNU MCSim
2.7.6.8 WebPlotDigitizer
2.8 Regulatory Perspectives of PK Modeling
2.9 Future Directions of PK Modeling
2.10 Conclusion
Abbreviations
References
Chapter 3 Physiologically Based Pharmacokinetic Modeling
3.1 Introduction
3.2 Significance of PBPK Modeling
3.3 Principles for the Development of PBPK for Special Populations
3.4 Data Integration for Special Populations
3.4.1 Demographic Data
3.4.2 Physiological Consideration
3.4.3 Ontogeny
3.4.4 Age and Maturation Changes
3.4.5 Steady State Volume of Distribution (Vdss)
3.5 Applications of PBPK Modeling
3.5.1 Dose Optimization/Regimen/Selection
3.5.2 Dose Individualization/Precision Dosing
3.5.3 Biopharmaceutics
3.6 Regulatory Applications/Pre-Post Market Utilization
3.7 Case Studies
3.7.1 Simulation Application
3.7.2 Successful Applications
3.8 Lessons Learned
3.9 Conclusion
References
Chapter 4 Therapeutic Drug Monitoring in Special Populations
4.1 Introduction
4.2 Pediatrics
4.2.1 Importance of TDM in Pediatrics
4.2.2 Pharmacokinetic Differences in Pediatric Patients
4.2.3 Drug Absorption in the Pediatric Population
4.2.4 Drug Distribution in the Pediatric Population
4.2.5 Drug Metabolism and Elimination in the Pediatric Population
4.3 TDM Practices in Pediatrics
4.3.1 Vancomycin
4.3.2 Aminoglycosides
4.3.3 Ganciclovir/Valganciclovir
4.3.4 Antiepileptic Drugs (AEDs)
4.3.5 Enoxaparin
4.4 Conclusion
4.5 Pregnancy
4.5.1 Physiological Adaptations in Pregnancy
4.5.2 Current State of Clinical Practice of TDM in Pregnancy
4.5.3 TDM in Pregnancy
4.5.3.1 Antiepileptics
4.5.3.2 Antidepressants
4.5.3.3 Antiretroviral Drugs
4.5.3.4 Immunomodulatory Drugs
4.5.4 Challenges in the Implementation of TDM in the Pregnant Population
4.6 The Elderly
4.6.1 Physiological Changes in the Elderly
4.6.2 Effect of Aging on Drug Pharmacokinetics
4.6.3 Application of TDM in the Elderly
4.6.3.1 Cardiac Glycosides
4.6.3.2 Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)
4.6.3.3 Anticoagulants
4.6.3.4 Benzodiazepines
4.7 Conclusion
4.8 Hepatic and Renal Impairments
4.8.1 Hepatic Impairment
4.8.2 TDM in Patients with Hepatic Impairment
4.8.2.1 Meropenem
4.8.2.2 Metoprolol
4.8.2.3 Midazolam
4.8.3 Renal Impairment
4.8.4 Prerenal Disease
4.8.5 Intrinsic Renal Vascular Disease
4.8.6 Intrinsic Glomerular Disease (Nephritic or Nephrotic)
4.8.7 TDM in Renal Impairment
4.8.7.1 Vancomycin
4.8.7.2 Metformin
4.9 Conclusion
4.10 Overall Conclusion and Future Direction
Acknowledgment
References
Chapter 5 Optimization of Drug Dosing Regimen
5.1 Introduction
5.2 Dosing Regimen Optimization Approaches and Strategies
5.2.1 Models Used for Dosing Regimen Selection
5.2.1.1 Pharmacometric Models
5.2.1.2 PK Models
5.2.1.3 Empirical Dose-Response Models
5.2.1.4 Multiple Comparison Procedures Models (MCP-Mod)
5.2.1.5 Model Averaging
5.2.2 Role of Patient Characteristics in Dose Selection
5.2.2.1 Phenotype-GuidedDosing
5.2.2.2 Genotype-GuidedDrug Dosing
5.2.3 Therapeutic Drug Monitoring (TDM)
5.3 Dosing Regimen in Special Populations
5.3.1 Dosing Regimen in Cancer Patients
5.3.1.1 Metronomic Chemotherapy
5.3.2 Dosing Regimen for Patients on Antimicrobial Therapy
5.3.2.1 Antimicrobial Stewardship Strategy
5.3.2.2 Mathematical Models for Optimizing Antimicrobial Therapy
5.3.2.3 Antimicrobial Dosing Strategies During CRRT
5.3.2.4 Methods for Enhancing Dosing of Antimicrobials via Nebulization
5.3.3 Dosing Regimen in Pediatric Patients
5.3.3.1 Physiological Differences Between Pediatric and Adult Patients
5.3.3.2 Application of MIDD in Pediatric Dose Selection
5.3.3.3 Scaling from Adults to Pediatric Patients
5.3.3.4 Scaling from Animals to Pediatric Patients
5.3.3.5 Integrating Mechanistic Models in Neonates and Infants
5.3.3.6 Dose Optimization in Neonates and Infants
5.4 Conclusion
References
Chapter 6 Artificial Intelligence in Drug Development
6.1 Introduction
6.2 Application of AI in Drug Design
6.2.1 Target Identification and Validation
6.2.2 Drug Candidate Design and Optimization
6.2.3 Virtual Screening and Molecular Docking
6.2.4 Synthesis Planning
6.2.5 Predicting Drug Toxicity and Pharmacokinetics
6.2.6 Personalized Medicine
6.3 AI Use in Drug Formulation
6.4 Drug Release Characterization Using AI
6.5 AI-Based Dose/Dosing Regimen
6.6 Dissolution Rate Predictions with AI
6.7 Clinical End-Point Evaluation with AI
6.8 AI in Prediction of Fate of Drugs Administered Via Mucosal, Transdermal, and Parenteral Routes
6.9 AI-Integrated Mechanistic Modeling Platform for Drug Delivery and Monitoring
6.10 AI-Based Tools for Metabolism and Clearance Prediction
6.11 Limitations of Existing Tools
6.12 Conclusions
6.13 Conflict of Interest
Acknowledgments
References
Chapter 7 Drug Disposition in Neonates and Infants
7.1 Introduction
7.2 Drug Absorption in Neonates and Infants
7.3 Drug Distribution in Neonates and Infants
7.4 Hepatic Metabolism of Drugs in Neonates and Infants
7.4.1 Phase I Metabolism
7.4.2 Phase II Metabolism
7.5 Drug Excretion in Neonates and Infants
7.6 Pharmacodynamics in Neonates and Infants
7.7 Age-Related Dosing Regimen in Neonates and Infants
7.8 Conclusion
References
Chapter 8 Drug Disposition in Adolescents
8.1 Introduction
8.2 Physiological Considerations in Adolescents
8.2.1 Organ Development: Liver and Kidney Maturation
8.2.2 Variations in Body Composition
8.2.3 Hormonal Changes
8.2.3.1 Males
8.2.3.2 Females
8.2.4 Other Physiological Changes
8.3 Medication Adherence Challenges in Adolescents
8.4 Psychological Development on Drug Disposition
8.5 Risk-Taking behaviors and Their Implications on Medication Use
8.6 Drug Use Among Adolescents
8.6.1 Acetaminophen Use in Adolescents
8.6.2 Antidepressant Use in Adolescents
8.6.3 Drugs for ADHD
8.7 Pharmacokinetic Variability in Adolescents Drug Examples
8.7.1 Acetaminophen
8.7.2 Theophylline
8.7.3 Antidepressants
8.7.4 Drugs for ADHD
8.8 Legal and Ethical Considerations
8.8.1 Consent and Confidentiality in Adolescent Healthcare
8.8.2 Involving Adolescents in Treatment Decisions
8.8.3 Regulatory Aspects of Adolescents Drug Prescribing
8.9 Conclusion
References
Chapter 9 Drug Disposition in Pregnancy
9.1 Introduction
9.2 Physiological Changes in Pregnancy
9.2.1 Changes in Absorption
9.2.2 Changes in Distribution and Free Medication
9.2.3 Changes in Cytochrome Metabolism
9.2.4 Changes in Renal Excretion
9.2.5 General Considerations in Drug Dosing with Pregnancy
9.3 Placental Drug Disposition
9.3.1 Placental Barrier Anatomy and Physiology
9.3.2 Placental Transport Mechanisms
9.3.3 Methods of Study for Placental Drug Transfer
9.4 Drug Classification in Pregnancy
9.5 Pharmacokinetic (PK) Modeling
9.6 Physiologically Based Pharmacokinetic (PBPK) Modeling
9.7 Limitations in PK and PBPK Models
9.8 PBPK Model Variables
9.9 Determining Treatment During Pregnancy
9.10 Fetal Blood Flow and Drug Processing
9.10.1 Hepatic and Renal Processing
9.10.2 Embryonic Staging
9.11 Teratogens
9.11.1 Thalidomide
9.11.2 Alcohol
9.11.3 Smoking and E-cigarettes
9.11.4 Caffeine
9.11.5 Antibiotics
9.11.6 Retinoids
9.12 Conclusion
Abbreviations
References
Chapter 10 Drug Disposition in Obesity
10.1 Introduction
10.2 Index of Obesity
10.3 Pathogenesis of Obesity/Overweight
10.4 Drug Disposition in Obesity
10.4.1 Absorption
10.4.2 Distribution
10.4.3 Metabolism
10.4.4 Renal Excretion
10.5 Drug Dose Calculations in Obese Patients
10.5.1 Volume of Distribution (Vd)
10.5.2 Drug Clearance
10.5.3 Body Size Description
10.5.4 Drug Dose Calculation
10.6 Disposition of Drugs in Obesity
10.6.1 Volatile Agents
10.6.2 Thiopental
10.6.3 Propofol
10.6.4 Midazolam
10.6.5 Acetaminophen
10.6.6 Opioids
10.6.7 Unfractionated Heparin
10.6.8 Cephazolin
10.6.9 Enoxaparin
10.7 Conclusion
References
Chapter 11 Drug Disposition in Critical Care Patients
11.1 Introduction
11.2 Pharmacokinetic Considerations in Critical Care Patients
11.2.1 Drug Absorption Considerations in Critical Care Patients
11.2.2 Drug Distribution Considerations in Critical Care Patients
11.2.3 Drug Metabolism Considerations in Critical Care Patients
11.2.4 Drug Excretion Considerations in Critical Care Patients
11.3 Dosing Algorithms for Commonly Administered Drugs in Critical Care Patients
11.3.1 Antibacterial and Antifungal Agents
11.3.1.1 Aminoglycosides
11.3.1.2 ß-LactamAntibiotics
11.3.1.3 Fluoroquinolones
11.3.1.4 Oxazolidinones
11.3.1.5 Antifungal Agents
11.3.2 Inotropes
11.3.3 Antiviral Drugs
11.3.4 Narcotic Analgesics
11.3.4.1 Morphine and Pethidine
11.3.4.2 Fentanyl and Derivatives
11.3.5 Sedatives and Hypnotics
11.3.5.1 Midazolam
11.3.5.2 Lorazepam
11.3.6 Neuromuscular Blockers
11.4 Conclusion
References
Chapter 12 Drug Disposition in Renal Insufficiency
12.1 Renal Physiology
12.1.1 General Anatomical Structure
12.1.2 General Function of the Nephron
12.1.3 Water Regulation
12.1.4 Glomerular Filtration Rate (GFR)
12.1.5 Acid-Base Regulation
12.2 Glomerular Filtration Rate
12.3 Acute Kidney Injury
12.3.1 Diagnostic Criteria and Classification
12.3.2 Causes of AKI
12.3.3 Prerenal
12.3.4 Intrinsic
12.3.5 Postrenal
12.4 Chronic Kidney Disease
12.4.1 Diagnostic Criteria and Classification
12.4.2 Causes of Chronic Kidney Disease
12.5 Medication Dosing Modifications
12.5.1 Medication Dosing in Patients with CKD
12.5.2 Medications to Treat CKD-Induced HTN and Medications to Avoid in CKD
12.5.2.1 Antihypertensives
12.5.2.2 Hypoglycemics
12.5.2.3 Antimicrobials
12.5.2.4 Statins
12.5.2.5 NSAIDs
12.5.2.6 Analgesics
12.6 Epidemiology and Outcomes of Patients with CKD
References
Chapter 13 Drug Disposition in Hepatic Insufficiency
13.1 Introduction
13.2 The Spectrum of Liver Diseases
13.3 Liver Function and Drug Metabolism
13.3.1 Impact of Hepatic Insufficiency on Drug Metabolism
13.3.2 Pharmacokinetic Changes in Hepatic Insufficiency
13.3.3 Effect of Liver Diseases on Pharmacokinetics of Drugs
13.4 Dosing Algorithms in Clinical Practice
13.4.1 Drug Selection
13.4.2 Dosing Adjustments
13.4.3 Pharmacokinetic Considerations
13.5 Drug Disposition and Factors That Influence Drug Disposition
13.6 Major Classes of Drugs and Hepatic Insufficiency
13.6.1 Anticoagulants
13.6.2 Antibiotics
13.6.3 Analgesics
13.6.4 Anticonvulsants
13.6.5 Antidepressants
13.6.6 Antiretrovirals
13.7 Cases Demonstrating Application of Dosing Algorithms
13.7.1 Case 1: Warfarin for Anticoagulation
13.7.1.1 The Use of Warfarin in a Patient with Hereditary Bleeding Disorder
13.7.1.2 Dosing Algorithm of Warfarin
13.7.2 Case 2: Acetaminophen for Pain Management
13.7.2.1 Dosing Algorithm for Paracetamol and Other Cytochrome p450 Enzyme-inducing Drugs in Hepatic Insufficiency Using Child-Pugh Score
13.7.3 Case 3: Valproic Acid for Seizure Control
13.7.4 Case 4: Metronidazole for Infection
13.7.5 Case 5: Efavirenz for HIV Treatment
13.8 Limitations of Current Dosing Strategies
13.9 Conclusion and Future Perspectives
13.9.1 Emerging Technologies and Precision Medicine
13.9.2 Potential Impact of Pharmacogenomics
13.9.3 Areas of Research Interest
References
Chapter 14 Drug Disposition in Geriatrics
14.1 Introduction
14.2 Absorption
14.3 Distribution
14.4 Metabolism
14.5 Excretion
14.6 Hepatic
14.7 Renal
14.8 Cardiac
14.9 Sex Differences
14.10 Psychoactive Drugs
14.11 Anesthesiology Drugs
14.12 Drug Interactions
14.13 Drug Side Effects
14.14 Conclusion
Abbreviations
References
Chapter 15 Considerations and Regulatory Affairs for Clinical Research in Special Populations
15.1 Introduction
15.2 Regulatory Frameworks for Clinical Research in Special Populations
15.2.1 The Historical Evolution of Regulatory Frameworks for Special Population Research
15.2.2 Current Global Regulatory Frameworks for Special Population Research
15.2.3 Current Regional Regulations Concerning Clinical Research Involving Special Populations
15.2.3.1 The United States: Food and Drug Regulatory Authority (US FDA)
15.2.3.2 Europe: European Medicines Agency (EMA)
15.2.3.3 The United Kingdom: The Medicines and Healthcare Products Regulatory Agency (MHRA)
15.2.3.4 Australia: The Therapeutic Goods Administration (TGA)
15.2.3.5 Brazil: National Health Surveillance Agency (ANVISA)
15.2.3.6 India: Central Drugs Standard Control Organization (CDSCO)
15.2.3.7 China: National Medical Products Administration (NMPA)
15.2.3.8 South Africa: The South African Health Products Regulatory Authority (SAHPRA)
15.2.4 Holistic Analysis of Regional Regulations Concerning Clinical Research Involving Special Populations
15.3 Key Considerations for Clinical Trials in Special Population Groups
15.3.1 Pediatric Population Groups
15.3.1.1 Regulatory Guidelines Governing Pediatric Clinical Research
15.3.2 Regional Legislations Governing Clinical Research in Pediatric Populations
15.3.2.1 The United States: Food and Drug Regulatory Authority (US FDA)
15.3.2.2 Europe: European Medicines Agency (EMA)
15.3.2.3 The United Kingdom: The Medicines and Healthcare Products Regulatory Agency (MHRA)
15.3.2.4 India: Central Drugs Standard Control Organization (CDSCO)
15.3.2.5 Other Global Jurisdictions
15.3.3 Holistic Analysis of Regional Regulations Concerning Clinical Research Involving Pediatric Populations
15.3.4 Ethical Considerations for Clinical Research in Pediatric Populations
15.3.4.1 Assent and Informed Consent
15.3.4.2 Participant Recruitment
15.4 Pregnant Population Groups
15.4.1 Historical Exclusion of Pregnant Persons in Clinical Research
15.4.2 Regulatory Guidelines Governing Clinical Research in Pregnant Persons
15.4.3 Regional Legislations Governing Clinical Research in Pregnant Persons
15.4.3.1 The United States: Food and Drug Regulatory Authority (US FDA)
15.4.3.2 Europe: European Medicines Agency (EMA)
15.4.3.3 Australia: The Therapeutic Goods Administration (TGA)
15.4.3.4 Brazil: National Health Surveillance Agency (ANVISA)
15.4.3.5 India: Central Drugs Standard Control Organization (CDSCO)
15.4.3.6 China: National Medical Products Administration (NMPA)
15.4.4 Challenges and Barriers to Clinical Research in Pregnant Persons
15.5 Geriatric Populations
15.5.1 Key Regulatory Guidelines Governing Geriatric Clinical Research
15.5.2 Regional Legislations Governing Clinical Research in Geriatric Populations
15.5.2.1 The United States: Food and Drug Regulatory Authority (US FDA)
15.5.2.2 Europe: European Medicines Agency (EMA)
15.5.2.3 The United Kingdom: The Medicines and Healthcare Products Regulatory Agency (MHRA)
15.5.2.4 India: Central Drugs Standard Control Organization (CDSCO)
15.5.2.5 Other Global Jurisdictions
15.5.3 Challenges and Barriers to Clinical Research in Geriatric Populations
15.6 Critical Care
15.6.1 Key Regulatory Guidelines Governing Critical Care Clinical Research
15.6.2 Regional Legislations Governing Clinical Research in Critical Care Populations
15.6.2.1 The United States: Food and Drug Regulatory Authority (US FDA)
15.6.2.2 Europe: European Medicines Agency (EMA)
15.6.2.3 The United Kingdom: The Medicines and Healthcare Products Regulatory Agency (MHRA)
15.6.2.4 India: Central Drugs Standard Control Organization (CDSCO)
15.6.2.5 Other Global Jurisdictions
15.6.3 Challenges and Barriers to Clinical Research in Critical Care Populations
15.7 Summary Points
15.7.1 Regulatory Guidelines
15.7.2 Ethical Considerations
15.7.3 Participant Recruitment
15.8 Conclusion
References
Index
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