Drug-Drug Interactions for Therapeutic Biologics

Strategize, plan, and execute comprehensive drug-drug interaction assessments for therapeutic biologics

Offering both theory and practical guidance, this book fully explores drug-drug interaction assessments for therapeutic biologics during the drug development process. It draws together and analyzes all the latest findings and practices in order to present our current understanding of the topic and point the way to new research. Case studies and examples, coupled with expert advice, enable readers to better understand the complex mechanisms of biologic drug-drug interactions.

Drug-Drug Interactions for Therapeutic Biologics features contributions from leading international experts in all areas of therapeutic biologics drug development and drug-drug interactions. The authors' contributions reflect a thorough review and analysis of the literature as well as their own firsthand laboratory experience. Coverage includes such essential topics as:

• Drug-drug interaction risks in combination with small molecules and other biologics
• Pharmacokinetic and pharmacodynamic drug-drug interactions
• In vitro methods for drug-drug interaction assessment and prediction
• Risk-based strategies for evaluating biologic drug-drug interactions
• Strategies to minimize drug-drug interaction risk and mitigate toxic interactions
• Key regulations governing drug-drug interaction assessments for therapeutic biologics.

Drug-Drug Interactions for Therapeutic Biologics is recommended for pharmaceutical and biotechnology scientists, clinical pharmacologists, medicinal chemists, and toxicologists. By enabling these readers to understand how therapeutic biologics may interact with other drugs, the book will help them develop safer, more effective therapeutic biologics.

PREFACE ix

ABOUT THE EDITORS xi

CONTRIBUTORS xiii

1. DRUG INTERACTIONS FOR THERAPEUTIC PROTEINS: A JOURNEY JUST BEGINNING 1
Honghui Zhou and Bernd Meibohm

2. PHARMACOKINETIC AND PHARMACODYNAMIC-BASED DRUG INTERACTIONS FOR THERAPEUTIC PROTEINS 5
Dan Lu, Sandhya Girish, Frank-Peter Theil, and Amita Joshi

3. DRUG INTERACTION ASSESSMENT STRATEGIES: SMALL MOLECULES VERSUS THERAPEUTIC PROTEINS 39
Shannon Dallas, Carlo Sensenhauser, Souvik Chattopadhyay, and Jose Silva

4. MODEL-INDEPENDENT AND MODEL-BASED METHODS TO ASSESS DRUG–DRUG INTERACTIONS FOR THERAPEUTIC PROTEINS 63
Di Wu and Jeffrey S. Barrett

5. UTILITY OF IN VITRO METHODS IN DRUG–DRUG INTERACTION ASSESSMENT AND PREDICTION FOR THERAPEUTIC BIOLOGICS 73
Theresa Nguyen, Narendra Kishnani, and Raymond Evers

6. USE OF ANIMAL MODELS FOR PROJECTION OF CLINICAL DRUG–DRUG INTERACTIONS FOR THERAPEUTIC PROTEINS 103
Eugenia Kraynov and Martin E. Dowty

7. THE COCKTAIL APPROACH AND ITS UTILITY IN DRUG–DRUG INTERACTION ASSESSMENTS FOR THERAPEUTIC PROTEINS 111
Alexander Jetter and Uwe Fuhr

8. LOGISTIC CONSIDERATIONS IN STUDY DESIGN FOR BIOLOGIC DRUG–DRUGINTERACTION ASSESSMENTS 119
Min Zhu and Yu-Nien (Tom) Sun

9. STATISTICAL CONSIDERATIONS IN ASSESSING DRUG–DRUG INTERACTIONS FOR THERAPEUTIC BIOLOGICS 139
Chuanpu Hu and Honghui Zhou

10. SCIENTIFIC PERSPECTIVES ON THERAPEUTIC PROTEIN DRUG–DRUG INTERACTION ASSESSMENTS 155
Hong Zhao, Lei Zhang, Kellie Reynolds, and Shiew-Mei Huang

11. DISEASE–DRUG–DRUG INTERACTION ASSESSMENTS FOR TOCILIZUMAB—A MONOCLONAL ANTIBODY AGAINST INTERLEUKIN-6 RECEPTOR TO TREAT PATIENTS WITH RHEUMATOID ARTHRITIS 191
Xiaoping Zhang and Barbara J. Brennan

12. DRUG–DRUG INTERACTIONS FOR ETANERCEPT—A FUSION PROTEIN 207
Joan Korth-Bradley

13. DRUG INTERACTIONS OF CYTOKINES AND ANTICYTOKINE THERAPEUTIC PROTEINS 215
J. Greg Slatter, Larry C. Wienkers, and Leslie J. Dickmann

14. DRUG INTERACTIONS FOR GROWTH FACTORS AND HORMONES 239
Yow-Ming C. Wang and Tarundeep Kakkar

15. DRUG–DRUG INTERACTIONS FOR NUCLEIC ACID-BASED DERIVATIVES 257
Jian Wang and Hong Zhao

APPENDIX: MONOGRAPHS FOR DRUG-DRUGINTERACTIONS OF THERAPEUTICS BIOLOGICS 275
Jocelyn Leu, Simone Kasek, Christine Li, Wararat Limothai, Dora Babu Madhura, Chetan Rathi, Sumit Rawal, Josiah Ryman, Margaret Thomson, Ashit Trivedi, Honghui Zhou, and Bernd Meibohm

INDEX 351

HONGHUI ZHOU, PhD, is Senior Scientific Director and Janssen Fellow, Janssen Research & Development, LLC, Johnson & Johnson, where he heads the Pharmacokinetics & Pharma-codynamics Department within Biologics Clinical Pharmacology. Board-certified by the American Board of Clinical Pharmacology and an American College of Clinical Pharmacology Fellow, Dr. Zhou has authored more than 150 peer-reviewed scientific papers, book chapters, and conference abstracts in pharmacokinetics, pharmacodynamics, and drug-drug interactions.

BERND MEIBOHM, PhD, is Professor of Pharmaceutical Sciences and Associate Dean for Research and Graduate Programs at the College of Pharmacy, The University of Tennessee Health Science Center. Dr. Meibohm is a Fellow of the American Association of Pharmaceutical Scientists and the American College of Clinical Pharmacology.