ADME and Translational Pharmacokinetics / Pharmacodynamics of Therapeutic Proteins E-Book

Honghui Zhou

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Veröffentlichungsjahr: 2015

Beschreibung

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

Leseprobe

Table of Contents

COVER

TITLE PAGE

LIST OF CONTRIBUTORS

FOREWORD

1 ADME FOR THERAPEUTIC BIOLOGICS

1.1 INTRODUCTION

1.2 SM DRUG DISCOVERY AND DEVELOPMENT: HISTORICAL PERSPECTIVE

1.3 LM DRUG DISCOVERY AND DEVELOPMENT

1.4 CONCLUSIONS

REFERENCES

2 PROTEIN ENGINEERING

2.1 INTRODUCTION

2.2 METHODS OF PROTEIN ENGINEERING

2.3 APPLICATIONS OF PROTEIN ENGINEERING TO NON-ANTIBODY THERAPEUTIC PROTEINS

2.4 APPLICATIONS OF PROTEIN ENGINEERING TO THERAPEUTIC ANTIBODIES

2.5 FUTURE PERSPECTIVES

REFERENCES

3 THERAPEUTIC ANTIBODIES—PROTEIN ENGINEERING TO INFLUENCE ADME, PK, AND EFFICACY

3.1 INTRODUCTION

3.2 RELATIONSHIP BETWEEN pI AND PHARMACOKINETICS

3.3 NONSPECIFIC/SPECIFIC OFF-TARGET BINDING

3.4 pH-DEPENDENT ANTIGEN BINDING TO REDUCE TARGET-MEDIATED ELIMINATION

3.5 SOLUBLE ANTIGEN SWEEPING

3.6 FUTURE PERSPECTIVES

REFERENCES

4 ADME FOR THERAPEUTIC BIOLOGICS

4.1 INTRODUCTION

4.2 ANTIBODY–DRUG CONJUGATES

4.3 BISPECIFICS

4.4 CONCLUSIONS

REFERENCES

5 OVERVIEW OF ADME AND PK/PD OF ADCs

5.1 INTRODUCTION TO ADC

5.2 ABSORPTION

5.3 DISTRIBUTION

5.4 METABOLISM/CATABOLISM

5.5 DRUG-LINKER STABILITY

5.6 ELIMINATION

5.7 CLINICAL PK

5.8 PK AND PK/PD MODELING FOR ADCS

5.9 SUMMARY

REFERENCES

6 ROLE OF LYMPHATIC SYSTEM IN SUBCUTANEOUS ABSORPTION OF THERAPEUTIC PROTEINS

6.1 INTRODUCTION

6.2 PHYSIOLOGY OF SUBCUTANEOUS TISSUE

6.3 INTERSTITIAL TRANSPORT FROM SC INJECTION SITE

6.4 RELATIVE ROLE OF BLOOD AND LYMPHATIC SYSTEMS IN SC ABSORPTION

6.5 PRESYSTEMIC CATABOLISM IN SC ABSORPTION OF PROTEINS

6.6 EFFECT OF INJECTION SITE ON SC ABSORPTION

6.7 CONCLUSIONS

REFERENCES

7 BIODISTRIBUTION OF THERAPEUTIC BIOLOGICS

7.1 INTRODUCTION

7.2 DETERMINANTS OF ANTIBODY BIODISTRIBUTION

7.3 METHODS OF MEASURING ANTIBODY BIODISTRIBUTION

7.4 INTERPRETATION OF BIODISTRIBUTION DATA

7.5 CONCLUDING REMARKS

ACKNOWLEDGMENTS

REFERENCES

8 PREDICTION OF HUMAN PHARMACOKINETICS FOR PROTEIN-BASED BIOLOGIC THERAPEUTICS

8.1 INTRODUCTION

8.2 GENERAL ALLOMETRIC SCALING AND INTERSPECIES SCALING METHODS

8.3 CONSIDERATIONS FOR INTERSPECIES SCALING OF PROTEIN-BASED BIOLOGIC THERAPEUTICS

8.4 PHYSIOLOGICALLY BASED PK MODELING

8.5 PERSPECTIVES BEYOND THE PREDICTION

8.6 CONCLUSIONS

REFERENCES

9 FIXED DOSING VERSUS BODY-SIZE-BASED DOSING FOR THERAPEUTIC BIOLOGICS—A CLINICAL PHARMACOLOGY STRATEGY

9.1 INTRODUCTION

9.2 CONCLUSIONS

REFERENCES

10 IMPACT OF DISEASES, COMORBIDITY, AND TARGET PHYSIOLOGY ON ADME, PK, AND PK/PD OF THERAPEUTIC BIOLOGICS

10.1 INTRODUCTION

10.2 IMPACT OF DISEASES AND COMORBIDITY ON ADME AND PK OF THERAPEUTIC BIOLOGICS

10.3 IMPACT OF DISEASE AND TARGET PHYSIOLOGY ON PK AND PK/PD OF THERAPEUTIC BIOLOGICS

10.4 CORRELATION BETWEEN THE PK OF THERAPEUTIC BIOLOGICS AND TREATMENT RESPONSE

10.5 OTHER PATIENT CHARACTERISTICS THAT CAN IMPACT THE TREATMENT RESPONSE OF THERAPEUTIC BIOLOGICS

10.6 THE INTERPLAY BETWEEN DISEASE, TARGET PHYSIOLOGY, AND PK/PD OF THERAPEUTIC BIOLOGICS: CASE EXAMPLES

10.7 CONCLUDING REMARKS

ACKNOWLEDGMENTS

REFERENCES

11 IMMUNOGENICITY: ITS IMPACT ON ADME OF THERAPEUTIC BIOLOGICS

11.1 INTRODUCTION

11.2 IMMUNOGENICITY OF THERAPEUTIC BIOLOGICS

11.3 IMPACT OF ADA ON ADME

11.4 HOW TO DEAL WITH ADME CONSEQUENCES OF IMMUNE RESPONSES?

11.5 SUMMARY AND CONCLUSIONS

REFERENCES

12 MECHANISTIC PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELS IN DEVELOPMENT OF THERAPEUTIC MONOCLONAL ANTIBODIES

12.1 BACKGROUND

12.2 HISTORY

12.3 PRINCIPLES AND METHODS

12.4 CHALLENGES

12.5 SIMPLIFIED PBPK MODELS FOR mAbs

12.6 PERSPECTIVES

ACKNOWLEDGMENTS

REFERENCES

13 INTEGRATED QUANTITATION OF BIOTHERAPEUTIC DRUG–TARGET BINDING, BIOMARKERS, AND CLINICAL RESPONSE TO SUPPORT RATIONAL DOSE REGIMEN SELECTION

13.1 INTRODUCTION

13.2 METHODS

13.3 RESULTS AND DISCUSSION

13.4 CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

14 TARGET-DRIVEN PHARMACOKINETICS OF BIOTHERAPEUTICS

14.1 INTRODUCTION

14.2 SOLUBLE AND MEMBRANE-BOUND TARGETS

14.3 WHOLE-BODY TARGET-MEDIATED DRUG DISPOSITION MODELS AND THEIR APPROXIMATIONS

14.4 CELL-LEVEL TARGET-MEDIATED DRUG DISPOSITION MODELS

14.5 SIMPLIFIED PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR mAbs

14.6 CONCLUSION: LOOKING AT DATA THROUGH MODELS

ACKNOWLEDGMENT

REFERENCES

15 TARGET-DRIVEN PHARMACOKINETICS OF BIOTHERAPEUTICS

15.1 INTRODUCTION

15.2 PEPTIDE–Fc FUSION PROTEINS

15.3 MONOCLONAL ANTIBODIES (mAbs)

15.4 PARAMETERS CONTROLLING TARGET-DRIVEN NONLINEAR PHARMACOKINETICS OF BIOTHERAPEUTICS

15.5 IMPACT OF TARGET-DRIVEN NONLINEAR PHARMACOKINETICS OF BIOTHERAPEUTICS ON HALOMETRIC SCALING

15.6 CONCLUSIONS AND PERSPECTIVES

REFERENCES

16 TUMOR EFFECT-SITE PHARMACOKINETICS

16.1 INTRODUCTION

16.2 TUMOR PHARMACOKINETICS

16.3 IMPACT OF TUMOR PHARMACOKINETICS ON EFFICACY

16.4 CONCLUSIONS

REFERENCES

17 BRAIN EFFECT SITE PHARMACOKINETICS

17.1 CYTOTIC PROCESSES AT THE BBB

17.2 RECEPTORS AT THE BBB AS TARGETS FOR BIOLOGICS

17.3 “TROJAN HORSE” APPROACHES TO TARGET BBB RECEPTORS

17.4 COLLOIDAL CARRIERS FOR DRUG DELIVERY

17.5 OTHER BRAIN-DIRECTED CARRIERS

17.6 STEM CELL-MEDIATED DRUG DELIVERY

17.7 FOCUSED ULTRASOUND AND MICROBUBBLES

17.8 CONCLUSIONS AND PERSPECTIVES

REFERENCES

18 MOLECULAR PATHOLOGY TECHNIQUES IN THE PRECLINICAL DEVELOPMENT OF THERAPEUTIC BIOLOGICS

18.1 INTRODUCTION

18.2 TARGET EXPRESSION PROFILING

18.3 OFF-TARGET BINDING OF THE THERAPEUTIC BIOLOGIC REAGENT

18.4 BIODISTRIBUTION OF THERAPEUTIC BIOLOGIC REAGENT

18.5 DISCUSSION

18.6 CONCLUSION

REFERENCES

19 LABELING AND IMAGING TECHNIQUES FOR QUANTIFICATION OF THERAPEUTIC BIOLOGICS

19.1 INTRODUCTION

19.2 NEW AND CONVENTIONAL METHODSFOR LABELING OF BIOLOGICS

19.3 MOLECULAR IMAGING FOR THE STUDY OF PK AND BIODISTRIBUTION OF BIOLOGICS

19.4 CONCLUSIONS AND PERSPECTIVES

REFERENCES

20 KNOWLEDGE OF ADME OF THERAPEUTIC PROTEINS IN ADULTS FACILITATES PEDIATRIC DEVELOPMENT

20.1 INTRODUCTION

20.2 COMPARATIVE EVALUATION OF ADME OF THERAPEUTIC PROTEINS BETWEEN ADULTS AND CHILDREN

20.3 EXTRAPOLATION OF EFFICACY FROM ADULTS TO PEDIATRIC PATIENTS

20.4 PEDIATRIC DOSE STRATEGIES

20.5 SAMPLE-SIZE DETERMINATION FOR PEDIATRIC STUDIES

20.6 MODELING AND SIMULATION IN PEDIATRIC DRUG DEVELOPMENT FACILITATED BY EXISTING ADULT MODELS

20.7 FUTURE DIRECTIONS

REFERENCES

21 LC/MS VERSUS IMMUNE-BASED BIOANALYTICAL METHODS IN QUANTITATION OF THERAPEUTIC BIOLOGICS IN BIOLOGICAL MATRICES

21.1 INTRODUCTION

21.2 COMPARISON OF THE CHARACTERISTICS IN METHOD DEVELOPMENT

21.3 COMPARISON OF ASSAY PERFORMANCE

21.4 APPLICATION OF LBA AND LC/MS IN THE ANALYSIS OF THERAPEUTIC PROTEINS

21.5 SUMMARY AND FUTURE PERSPECTIVE

REFERENCES

22 BIOSIMILAR DEVELOPMENT: NONCLINICAL AND CLINICAL STRATEGIES AND CHALLENGES WITH A FOCUS ON THE ROLE OF PK/PD ASSESSMENTS

22.1 INTRODUCTION

22.2 ASPECTS OF BIOSIMILARITY

22.3 BIOSIMILARS’ REGULATORY/HISTORICAL PERSPECTIVE

22.4 NONCLINICAL ASSESSMENTS IN THE DEVELOPMENT OF BIOSIMILARS

22.5 CLINICAL PK AND PD ASSESSMENTS IN THE DEVELOPMENT OF BIOSIMILARS

22.6 CONCLUDING REMARKS

ACKNOWLEDGMENTS

REFERENCES

23 ADME PROCESSES IN VACCINES AND PK/PD APPROACHES FOR VACCINATION OPTIMIZATION

23.1 INTRODUCTION

23.2 BIOPHARMACEUTIC CONSIDERATIONS ON VACCINE ADME PROCESSES

23.3 VACCINES AND ADME PROCESSES

23.4 MATHEMATICAL MODELING FOR VACCINE OPTIMIZATION IN CANCER TREATMENT

23.5 SYSTEMS VACCINOLOGY: APPLICATION OF SYSTEMS BIOLOGY IN PERSONALIZED VACCINATION

23.6 CONCLUDING REMARKS

REFERENCES

24 DRUG DEVELOPMENT STRATEGIES FOR THERAPEUTIC BIOLOGICS: INDUSTRY PERSPECTIVES

24.1 INTRODUCTION

24.2 PRECLINICAL DEVELOPMENT

24.3 CLINICAL DEVELOPMENT

24.4 BIOSIMILARS

24.5 EMERGING MARKETS

24.6 CONCLUSIONS

REFERENCES

25 REVIEW: THE CRITICAL ROLE OF CLINICAL PHARMACOLOGY IN THE DEVELOPMENT OF BIOLOGICS

25.1 INTRODUCTION

25.2 PK AND PD OF BIOLOGICS

25.3 CRITICAL ROLE OF CLINICAL PHARMACOLOGY AND RELATED REGULATORY GUIDANCE FOR BIOLOGICS DEVELOPMENT

25.4 MODEL-BASED DRUG DEVELOPMENT FOR BIOLOGICS

25.5 CONCLUSIONS

25.6 DISCLAIMER

REFERENCES

26 INVESTIGATING THE NONCLINICAL ADME AND PK/PD OF AN ANTIBODY–DRUG CONJUGATE: A CASE STUDY OF ADO-TRASTUZUMAB EMTANSINE (T-DM1)

26.1 INTRODUCTION

26.2 IMPORTANCE OF ADME FOR ADCs

26.3 T-DM1 BIOANALYTICAL STRATEGY AND METHODS

26.4

EX VIVO

LINKER STABILITY

26.5 PLASMA PK

26.6 DISTRIBUTION OF T-DM1

26.7 T-DM1 CATABOLISM AND ELIMINATION

26.8 T-DM1 NONCLINICAL PK/PD

26.9 CONCLUSIONS

REFERENCES

27 USE OF PK/PD KNOWLEDGE IN GUIDING BISPECIFIC BIOLOGICS RESEARCH AND DEVELOPMENT

27.1 INTRODUCTION

27.2 STRUCTURAL FORMATS AND GENERATION OF BISPECIFIC BIOLOGICS

27.3 BIOCHEMISTRY ANDPHARMACOLOGY OF BISPECIFICS

27.4 PHARMACOKINETICS

27.5 PHARMACOKINETIC–PHARMACODYNAMIC MODEL-INFORMED DESIGN OF bsAbs