Systems Pharmacology and Pharmacodynamics PDF
Preview Systems Pharmacology and Pharmacodynamics
AAPS Advances in the Pharmaceutical Sciences Series 23 Donald E. Mager Holly H.C. Kimko Editors Systems Pharmacology and Pharmaco- dynamics AAPS Advances in the Pharmaceutical Sciences Series Volume 23 Editors-in-chief Daan J.A. Crommelin, Utrecht University, Utrecht, Utrecht, The Netherlands Robert A. Lipper, Back Cove Pharma, LLC, Waldoboro, ME, USA The AAPS Advances in the Pharmaceutical Sciences Series, published in partnership with the American Association of Pharmaceutical Scientists, is designed to deliver volumes authored by opinion leaders and authorities from around the globe, addressing innovations in drug research and development, and best practice for scientists and industry professionals in the pharma and biotech industries. More information about this series at http://www.springer.com/series/8825 Donald E. Mager Holly H.C. Kimko (cid:129) Editors Systems Pharmacology and Pharmacodynamics 123 Editors Donald E.Mager HollyH.C. Kimko Department ofPharmaceutical Sciences GlobalClinical Pharmacology University at Buffalo, SUNY Janssen Research & Development, LLC, Buffalo, NY SpringHouse,PA USA USA ISSN 2210-7371 ISSN 2210-738X (electronic) AAPS Advances inthe Pharmaceutical SciencesSeries ISBN978-3-319-44532-8 ISBN978-3-319-44534-2 (eBook) DOI 10.1007/978-3-319-44534-2 LibraryofCongressControlNumber:2016948099 ©AmericanAssociationofPharmaceuticalScientists2016 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpart of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission orinformationstorageandretrieval,electronicadaptation,computersoftware,orbysimilarordissimilar methodologynowknownorhereafterdeveloped. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publicationdoesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexemptfrom therelevantprotectivelawsandregulationsandthereforefreeforgeneraluse. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authorsortheeditorsgiveawarranty,expressorimplied,withrespecttothematerialcontainedhereinor foranyerrorsoromissionsthatmayhavebeenmade. Printedonacid-freepaper ThisSpringerimprintispublishedbySpringerNature TheregisteredcompanyisSpringerInternationalPublishingAG Theregisteredcompanyaddressis:Gewerbestrasse11,6330Cham,Switzerland Preface Systemspharmacology,arelativelynewdiscipline,istheinterfacebetweensystems biology and pharmacodynamics. It is a response to the growing awareness that pharmaceutical companies should reduce the high attrition in the pipeline due to insufficient efficacy or toxicity found in proof-of-concept and/or Phase 2 studies. Systems pharmacology provides a framework for integrating information obtained from understanding physiological/pathological pathways (normal body function systemvs.perturbedsystemduetodisease)andpharmacologicaltargetsinorderto predictclinicalefficacyandadverseeventsthroughiterationsbetweenmathematical modeling and experimentation. Two workshops on quantitative and systems pharmacology (QSP) were held at the NIH to discuss whether a merger of systems biology and pharmacology could advance the discovery, development, and clinical use of therapeutic drugs; the experts from academia, industry, and regulatory agencies have identified a need to integrate concepts and methods. Systems biology and pharmacodynamics have evolvedinparallel,althoughtherearesignificantinterrelationshipsthatcanenhance drug discovery and enable optimized therapy for each patient. Currently, no sin- glebook exists that covers the expertise from both systems biology and pharma- codynamics researchers. To that end, the intent of this book is to foster such dialogue by introducing systems modeling concepts to pharmacometricians and pharmaceutical scientists (Part I),introducingPK/PDprinciplestoengineers andsystems scientists(PartII), and providing detailed examples of systems pharmacology models from academia and the pharmaceutical industry that may be useful for developing drugs to treat various diseases (Part III). In addition, a perspective on the role of systems phar- macology modeling in regulatory drug approval is presented in Chap. 2, followed by the application of systems pharmacology in drug discovery and development from an industrial perspective (Chap. 3). This book will facilitate collaboration among industry, clinical, academic, and regulatory scientists so that systems pharmacology and pharmacodynamics may be developed and refined further to show practical applications in drug development. v vi Preface We hope that this book is informative and relevant to any researcher or prac- titioner who wants to use systems pharmacology and pharmacodynamics in the design, analysis, or regulatory decisions concerning drug discovery, as well as nonclinicaland clinical drugdevelopment. Thisbookdoesnotembrace all aspects of systems pharmacology and pharmacodynamics, nor is it intended as a technical recipefor how to apply them. Rather, it isa source ofinformation that enablesthe reader to gain a better understanding of the essential background and knowledge of the fields of systems pharmacology and pharmacodynamics. Thisbookwouldnotexistwithoutthehelpandencouragementofmanypeople. We are grateful to all the authors who contributed to the chapters. We also would liketothankourpublisher,AAPS/Springer,forthisopportunitytocontributetothe fields of systems pharmacology and pharmacodynamics. Buffalo, NY, USA Donald E. Mager Spring House, PA, USA Holly H.C. Kimko Contents Part I Systems Modeling 1 Systems Pharmacology and Pharmacodynamics: An Introduction.... .... ..... .... .... .... .... .... ..... .... 3 Donald E. Mager and Holly H.C. Kimko 2 Role of Systems Modeling in Regulatory Drug Approval..... .... 15 Vikram Sinha, Shiew-Mei Huang, Darrell R. Abernethy, Yaning Wang, Ping Zhao and Issam Zineh 3 Quantitative Systems Pharmacology: Applications and Adoption in Drug Development .... .... .... .... ..... .... 27 Saroja Ramanujan, Kapil Gadkar and Ananth Kadambi 4 Systems Pharmacology: An Overview ... .... .... .... ..... .... 53 Marc R. Birtwistle, Jens Hansen, James M. Gallo, Sreeharish Muppirisetty, Peter Man-Un Ung, Ravi Iyengar and Avner Schlessinger 5 Discrete Dynamic Modeling: A Network Approach for Systems Pharmacology . .... .... ..... .... .... .... .... .... ..... .... 81 Steven Nathaniel Steinway, Rui-Sheng Wang and Reka Albert 6 Kinetic Models of Biochemical Signaling Networks .... ..... .... 105 Mehdi Bouhaddou and Marc R. Birtwistle 7 Mechanistic Models of Physiological Control Systems .. ..... .... 137 Michael C.K. Khoo, Wen-Hsin Hu and Patjanaporn Chalacheva Part II Pharmacodynamics 8 Foundations of Pharmacodynamic Systems Analysis ... ..... .... 161 William J. Jusko vii viii Contents 9 Direct, Indirect, and Signal Transduction Response Modeling .... 177 Wojciech Krzyzanski 10 Irreversible Pharmacodynamics.... .... .... .... .... ..... .... 211 Alberto Russu and Italo Poggesi 11 Feedback Control Indirect Response Models . .... .... ..... .... 229 Yaping Zhang and David Z. D’Argenio 12 Nonlinear Mixed Effects Modeling in Systems Pharmacology . .... 255 Peter L. Bonate, Amit Desai, Ahsan Rizwan, Zheng Lu and Stacey Tannenbaum 13 Detecting Pharmacokinetic and Pharmacodynamic Covariates from High-Dimensional Data .. .... .... .... .... .... ..... .... 277 Jonathan Knights and Murali Ramanathan Part III Multi-scale Models of Drug Action 14 Multi-scale Modeling of Drug Action in the Nervous System.. .... 305 Hugo Geerts, Patrick Roberts, Athan Spiros and Robert Carr 15 Mechanistic Modeling of Inflammation .. .... .... .... ..... .... 325 Jeremy D. Scheff, Kubra Kamisoglu and Ioannis P. Androulakis 16 Systems Pharmacology of Tyrosine Kinase Inhibitor-Associated Toxicities . .... .... .... ..... .... .... .... .... .... ..... .... 353 Yoshiaki Kariya, Masashi Honma and Hiroshi Suzuki 17 Translational Modeling of Antibacterial Agents... .... ..... .... 371 Gauri G. Rao, Neang S. Ly, Brian T. Tsuji, Jürgen B. Bulitta and Alan Forrest 18 Viral Dynamic Modeling of Hepatitis C Virus Infection: Past Successes and Future Challenges... .... .... .... .... ..... .... 403 Eric L. Haseltine and Holly H.C. Kimko 19 Using Systems Pharmacology to Advance Oncology Drug Development .. .... .... ..... .... .... .... .... .... ..... .... 421 Daniel C. Kirouac 20 Systems Pharmacology Modeling in Type 2 Diabetes Mellitus. .... 465 James R. Bosley, Tristan S. Maurer and Cynthia J. Musante Index .... .... .... .... .... ..... .... .... .... .... .... ..... .... 509 Editors and Contributors About the Editors Donald E. Mager is a Professor of Pharmaceutical Sciences at the University at Buffalo,StateUniversityofNewYork.HealsoservedasaVisitingProfessoratthe University Paris Descartes in January from 2007–2013 and 2016. He currently serves on the Clinical Pharmacology Advisory Committee to the FDA and the Editorial Advisory Boards of several journals. Dr. Mager also serves as an AssociateorConsultingEditoratCPT:Pharmacometrics&SystemsPharmacology (CPT:PSP), Journal of Pharmacology & Experimental Therapeutics (JPET), and Pharmacology, Research & Perspectives (PRP). He is a former President of the InternationalSocietyofPharmacometricsandisaFellowandmemberoftheBoard ofRegentsoftheAmericanCollegeofClinicalPharmacology.Inaddition,heisan expert member of the Board of Pharmaceutical Sciences at FIP and serves on the ScientificAdvisoryBoardtoSimcyp.Hisresearchfocusesonidentifyingmolecular and physiological factors that control the pharmacological properties of various drugs, with a focus on anti-cancer and immunomodulatory agents. He has con- tributed to 120+ peer-reviewed publications. Holly H.C. Kimko is a senior pharmacometrician in the Global Clinical Pharmacology department at Janssen Research & Development, LLC, Spring House, PA, and Adjunct Associate Professor in the Pharmacy School of Rutgers University, New Jersey. Dr. Kimko is a Janssen Research Fellow and American Association of Pharmaceutical Scientists Fellow. She championed the use of modelingandsimulationsindrugdevelopmentattheCenterforDrugDevelopment ScienceatGeorgetownUniversityMedicalSchool,Washington,DCin1995–2002. Trained in biochemistry and pharmacy, Dr. Kimko earned her Ph.D. degree in pharmaceutical sciences from the University at Buffalo, State University of New York. She has published key papers on physiologically-based indirect response modelingandapplicationsofclinicaltrialsimulationsandhaseditedtwobookson ix
The list of books you might like
