Honghui Zhou, Frank-Peter Theil

ADME and Translational Pharmacokinetics / Pharmacodynamics of Therapeutic Proteins (eBook, PDF)

Applications in Drug Discovery and Development

• Format: PDF

Produktbeschreibung

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

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Produktdetails

• Verlag: Jossey-Bass
• Erscheinungstermin: 26. Oktober 2015
• Englisch
• ISBN-13: 9781118898802
• Artikelnr.: 44024202

Autorenporträt

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).

Inhaltsangabe

LIST OF CONTRIBUTORS xvii

FOREWORD xix

1 ADME for Therapeutic Biologics: What Can We Leverage from Great Wealth of ADME Knowledge and Research for Small Molecules 1
Weirong Wang and Thomayant Prueksaritanont

1.1 Introduction 1

1.2 SM Drug Discovery and Development: Historical Perspective 1

1.3 LM Drug Discovery and Development 3

1.4 Conclusions 8

References 8

2 Protein Engineering: Applications to Therapeutic Proteins and Antibodies 13
Andrew G. Popplewell

2.1 Introduction 13

2.2 Methods of Protein Engineering 13

2.3 Applications of Protein Engineering to Non-Antibody Therapeutic Proteins 16

2.4 Applications of Protein Engineering to Therapeutic Antibodies 16

2.5 Future Perspectives 20

References 21

3 Therapeutic Antibodies--Protein Engineering to Influence ADME, PK, and Efficacy 25
Tatsuhiko Tachibana, Kenta Haraya, Yuki Iwayanagi and Tomoyuki Igawa

3.1 Introduction 25

3.2 Relationship between pI and Pharmacokinetics 26

3.3 Nonspecific/Specific Off?]Target Binding 27

3.4 pH?]Dependent Antigen Binding to Reduce Target?]Mediated Elimination 28

3.5 Soluble Antigen Sweeping 31

3.6 Future Perspectives 34

References 34

4 ADME for Therapeutic Biologics: Antibody?]Derived Proteins and Proteins with Novel Scaffolds 39
Chetan Rathi and Bernd Meibohm

4.1 Introduction 39

4.2 Antibody-Drug Conjugates 39

4.3 Bispecifics 45

4.4 Conclusions 50

References 50

5 Overview of ADME and PK/PD of ADCs 55
Baiteng Zhao and Tae H. Han

5.1 Introduction to ADC 55

5.2 Absorption 56

5.3 Distribution 58

5.4 Metabolism/Catabolism 58

5.5 Drug?]Linker Stability 59

5.6 Elimination 60

5.7 Clinical PK 60

5.8 PK and PK/PD Modeling for ADCs 61

5.9 Summary 62

References 63

6 Role of Lymphatic System in Subcutaneous Absorption of Therapeutic Proteins 67
Jiunn H. Lin and Weirong Wang

6.1 Introduction 67

6.2 Physiology of Subcutaneous Tissue 68

6.3 Interstitial Transport from SC Injection Site 68

6.4 Relative Role of Blood and Lymphatic Systems in SC Absorption 69

6.5 Presystemic Catabolism in SC Absorption of Proteins 72

6.6 Effect of Injection Site on SC Absorption 74

6.7 Conclusions 74

References 75

7 Biodistribution of Therapeutic Biologics: Methods and Applications in Informing Target Biology, Pharmacokinetics, and Dosing Strategies 77
Sean B. Joseph, Saileta Prabhu and C. Andrew Boswell

7.1 Introduction 77

7.2 Determinants of Antibody Biodistribution 77

7.3 Methods of Measuring Antibody Biodistribution 81

7.4 Interpretation of Biodistribution Data 85

7.5 Concluding Remarks 87

Acknowledgments 88

References 88

8 Prediction of Human Pharmacokinetics for Protein?]Based Biologic Therapeutics 91
Chao Han and Christina Lourdes Mayer

8.1 Introduction 91

8.2 General Allometric Scaling and Interspecies Scaling Methods 92

8.3 Considerations for Interspecies Scaling of Protein?]Based Biologic Therapeutics 93

8.4 Physiologically Based PK Modeling 100

8.5 Perspectives Beyond the Prediction 101

8.6 Conclusions 102

References 102

9 Fixed Dosing versus Body?]Size?]Based Dosing for Therapeutic Biologics--A Clinical Pharmacology Strategy 107
Diane D. Wang, Justin T. Hoffman and Kourosh Parivar

9.1 Introduction 107