ADME AND TRANSLATIONAL PHARMACOKINETICS / PHARMACODYNAMICS OF THERAPEUTIC PROTEINS.. APPLICATIONS IN DRUG DISCOVERY AND DEVELOPMENT

With an emphasis on the fundamental and practical aspects of ADME for therapeutic proteins, this book helps readers strategize, plan and implement translational research for biologic drugs.
• Details cutting-edge ADME (absorption, distribution, metabolism and excretion) and PKPD (pharmacokinetic / pharmacodynamics) modeling for biologic drugs.
• Combines theoretical with practical aspects of ADME in biologic drug discovery and development and compares innovator biologics with biosimilar biologics and small molecules with biologics, giving a lessons-learned perspective.
• Includes case studies about leveraging ADME to improve biologics drug development for monoclonal antibodies, fusion proteins, pegylated proteins, ADCs, bispecifics, and vaccines.
• Presents regulatory expectations and industry perspectives for developing biologic drugs in USA, EU, and Japan.
• Provides mechanistic insight into biodistribution and target-driven pharmacokinetics in important sites of action such as tumors and the brain.

Authors
• Honghui Zhou is a Senior Director and Janssen Fellow, at Janssen Research & Development, LLC and US head of Pharmacological and Translational Modeling. Board-certified by the American Board of Clinical Pharmacology and a Fellow of American Association of Pharmaceutical Scientists (AAPS) and American College of Clinical Pharmacology (ACCP), he has authored 200 peer-reviewed scientific papers, book chapters, and conference abstracts and co-edited the book Drug-Drug Interactions for Therapeutic Biologics (Wiley, 2013).
• Frank-Peter Theil heads nonclinical development at UCB Biopharma. Dr. Theil has authored and co-authored 40 research publications, three book chapters and he has given numerous invited presentations at national and international scientific meetings. He is a member of the American Association of Pharmaceutical Scientists (AAPS) and American Society of Clinical Pharmacology and Therapeutics (ASCPT).

Table of Contents
1 ADME for Therapeutic Biologics: What Can We Leverage from Great Wealth of ADME Knowledge and Research for Small Molecules 1
2 Protein Engineering: Applications to Therapeutic Proteins and Antibodies 13
3 Therapeutic Antibodies—Protein Engineering to Influence ADME, PK, and Efficacy 25
4 ADME for Therapeutic Biologics: Antibody ]Derived Proteins and Proteins with Novel Scaffolds 39
5 Overview of ADME and PK/PD of ADCs 55
6 Role of Lymphatic System in Subcutaneous Absorption of Therapeutic Proteins 67
7 Biodistribution of Therapeutic Biologics: Methods and Applications in Informing Target Biology, Pharmacokinetics, and Dosing Strategies 77
8 Prediction of Human Pharmacokinetics for Protein ]Based Biologic Therapeutics 91
9 Fixed Dosing versus Body ]Size ]Based Dosing for Therapeutic Biologics—A Clinical Pharmacology Strategy 107
10 Impact of Diseases, Comorbidity, and Target Physiology on ADME, PK, and PK/PD of Therapeutic Biologics 125
11 Immunogenicity: Its Impact on ADME of Therapeutic Biologics 147
12 Mechanistic Physiologically Based Pharmacokinetic
13 Integrated Quantitation of Biotherapeutic Drug–Target Binding, Biomarkers, and Clinical Response to Support Rational Dose Regimen Selection 175
14 Target ]Driven Pharmacokinetics of Biotherapeutics 197
15 Target ]Driven Pharmacokinetics of Biotherapeutics 213
16 Tumor Effect ]Site Pharmacokinetics: Mechanisms and Impact on Efficacy 225
17 Brain Effect Site Pharmacokinetics: Delivery of Biologics Across the Blood–Brain Barrier 241
18 Molecular Pathology Techniques in the Preclinical Development of Therapeutic Biologics 257
19 Labeling and Imaging Techniques for Quantification of Therapeutic Biologics 271
20 Knowledge of ADME of Therapeutic Proteins in Adults Facilitates Pediatric Development 295
21 LC/MS versus Immune ]Based Bioanalytical Methods in Quantitation of Therapeutic Biologics in Biological Matrices 313
22 Biosimilar Development: Nonclinical and Clinical Strategies and Challenges with a Focus on the Role of PK/PD Assessments 331
23 ADME Processes in Vaccines and PK/PD Approaches for Vaccination Optimization 347
24 Drug Development Strategies for Therapeutic Biologics: Industry Perspectives 369
25 Review: The Critical Role of Clinical Pharmacology in the Development of Biologics 385
26 Investigating the Nonclinical ADME and PK/PD of an Antibody–Drug Conjugate: A Case Study of ADO ]Trastuzumab Emtansine (T ]DM1) 401
27 Use of PK/PD Knowledge in Guiding Bispecific Biologics Research and Development 413