Nicht aus der Schweiz? Besuchen Sie lehmanns.de
Predictive ADMET - Jianling Wang, Laszlo Urban

Predictive ADMET

Integrated Approaches in Drug Discovery and Development
Buch | Hardcover
624 Seiten
2014
John Wiley & Sons Inc (Verlag)
978-1-118-29992-0 (ISBN)
CHF 227,60 inkl. MwSt
  • Versand in 10-15 Tagen
  • Versandkostenfrei
  • Auch auf Rechnung
  • Artikel merken
By guiding in the application of techniques and tools for predicting ADMET outcomes in drug candidates, Predictive ADMET offers a road map for drug discovery scientists to generate effective and safe drugs for unmet medical needs.
This book helps readers integrate in silico, in vitro, and in vivo ADMET (absorption, distribution, metabolism, elimination and toxicity) and PK (pharmacokinetics) data with routine testing applications so that pharmaceutical scientists can diagnose ADMET problems and present appropriate recommendations to move drug discovery programs forward.

The book introduces the current clinical practice for drug discovery and development along with the impact on early risk assessment; consolidates the tools and models to intelligently integrate existing in silico, in vitro and in vivo ADMET data; and demonstrates successful cases and lessons learned from real drug discovery and development. In short, it is a book aimed to provide a practical road map for drug discovery and development scientists to generate efficacious and safe drugs for unmet medical needs.

Jianling Wang is the Cambridge Head of Discovery ADME at Novartis Institutes for BioMedical Research. He has published over 40 journal papers, reviews, and book chapters and lectured at over 30 scientific conferences and courses. Laszlo Urban is the Executive Director for Preclinical Safety Profiling at Novartis Institutes for BioMedical Research. He has over 10 years of experience in academia and 20 years in the pharmaceutical industry. Among Dr. Urban’s publications are over 120 peer-reviewed scientific papers, 3 books including Hit and Lead Profiling: Identification and Optimization of Drug-like Molecules (Wiley, 2009).

Preface ix

Contributors xi

I Introduction to the Current Scientific, Clinical, and Social Environment of Drug Discovery and Development

1 Current Social, Clinical, and Scientific Environment of Pharmaceutical R&D 3
Laszlo Urban, Jean-Pierre Valentin, Kenneth I Kaitin, and Jianling Wang

2 Polypharmacology and Adverse Bioactivity Profiles Predict Potential Toxicity and Drug-related ADRs 23
Teresa Kaserer, Veronika Temml, and Daniela Schuster

II Intelligent Integration and Extrapolation of Admet Data

3 ADMET Diagnosis Models 49
Bernard Faller, Suzanne Skolnik, and Jianling Wang

4 PATH (Probe ADME and Test Hypotheses): A Useful Approach Enabling Hypothesis-driven ADME Optimization 63
Leslie Bell, Suzanne Skolnik, and Dallas Bednarczyk

5 PK-MATRIX—A Permeability: Intrinsic Clearance System for Prediction, Classification, and Profiling of Pharmacokinetics and Drug–drug Interactions 89
Urban Fagerholm

6 Maximizing the Power of a Local Model for ADMET-property Prediction 103
Sebastien Ronseaux, Jeremy Beck, and Clayton Springer

7 Chemoinformatic and Chemogenomic Approach to ADMET 125
Virginie Y. Martiny, Ilza Pajeva, Michael Wiese, Andrew M. Davis, and Maria A. Miteva

8 Multiparameter Optimization of ADMET for Drug Design 145
Matthew D. Segall and Edmund J. Champness

9 PBPK: Integrating In Vitro and In Silico Data in Physiologically Based Models 167
Hannah M. Jones and Neil Parrott

10 Emerging Full Mechanistic Physiologically Based Modeling 189
Kiyohiko Sugano

11 Pharmacokinetic/Pharmacodynamic Modeling in Drug Discovery: A Translational Tool to Optimize Discovery Compounds Toward the Ideal Target-specific Profile 211
Patricia Schroeder

III Assessment and Mitigation of Critical Clinically Relevant Admet Risks in Drug Discovery and Development

12 In Vitro–In Silico Tools to Predict Pharmacokinetics of Poorly Soluble Drug Compounds 235
Christian Wagner and Jennifer B. Dressman

13 Evaluation of the Collective Impact of Passive Permeability and Active Transport on In Vivo Blood-brain Barrier and Gastrointestinal Drug Absorption 263
Donna A. Volpe, Hong Shen, and Praveen V. Balimane

14 Integrated Assessment of Drug Clearance and Cross-Species Scalability 291
Kevin Beaumont, James R. Gosset, and Chris E. Keefer

15 Practical Anticipation of Human Efficacious Doses and Pharmacokinetics using Preclinical In Vitro and In Vivo Data 319
Tycho Heimbach, Rakesh Gollen, and Handan He

16 Management and Mitigation of Human Drug–drug Interaction Risks in the Drug Discovery and Development Phases 353
Heidi J. Einolf and Imad Hanna

17 Integrated Assessment and Clinical Translation of In Vitro Off-target Safety Pharmacology Risks 397
Patrick Y. Muller and Christian F. Trendelenburg

18 Integrated Risk Assessment of Cardiovascular Safety in Drug Discovery 407
Gül Erdemli and Ruth L. Martin

19 Drug-induced Hepatotoxicity: Advances in Preclinical Predictive Strategies and Tools 433
Donna M. Dambach

20 Carcinogenicity and Teratogenicity Assessment 467
Hans-Jörg Martus, David Beckman, and Lutz Mueller

21 Nephrotoxicity: Development of Biomarkers for Preclinical and Clinical Application 491
Frank Dieterle and Estelle Marrer

IV Success Stories and Lessons Learned

22 Early Intervention with Formulation Strategies for Multidimensional Problems to Optimize for Success 507
Stephanie Dodd, Christina Capacci-Daniel, Christopher Towler, Riccardo Panicucci, and Keith Hoffmaster

23 Cytochrome P450-mediated Drug Interaction and Cardiovascular Safety: The Seldane to Allegra Transformation 523
F. Peter Guengerich

24 Clinical Toxicity Profile of VEGF Inhibitors 535
Mark P. S. Sie and Ferry A. L. M. Eskens

25 Cardiomyopathy: Drug Induced and Predisposed 555
Shirley A. Aguirre and Eileen R. Blasi

26 Safety Management by Pharmacokinetic Considerations: Ranibizumab (Lucentis) and Bevacizumab (Avastin) 569
Nicole H. Siegel and Manju L. Subramanian

Index 583

Verlagsort New York
Sprache englisch
Maße 164 x 244 mm
Gewicht 989 g
Themenwelt Medizin / Pharmazie Medizinische Fachgebiete Pharmakologie / Pharmakotherapie
Naturwissenschaften Biologie Biochemie
Naturwissenschaften Chemie Analytische Chemie
Technik
ISBN-10 1-118-29992-2 / 1118299922
ISBN-13 978-1-118-29992-0 / 9781118299920
Zustand Neuware
Haben Sie eine Frage zum Produkt?
Mehr entdecken
aus dem Bereich