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. Featuring case studies and lessons learned from real drug discovery and development, the text: helps users diagnose ADMET problems; presents appropriate recommendations; introduces the current clinical practice for drug discovery and development; and consolidates the tools and models to intelligently integrate existing in silico, in vitro and in vivo ADMET data. INDICE: Part I: Introduction to the current scientific, clinical and social environment of drug discovery and development Preface Jianling Wang and Laszlo Urban 1. Current social, clinical and scientific environment of pharmaceutical R&D Laszlo Urban, Jean–Pierre Valentin, Kenneth I Kaitin and Jianling Wang 2. Polypharmacology and adverse bioactivity profiles predict potential toxicity and drug–related ADRs Teresa Kaserer, Veronika Temml and Daniela Schuster Part II: Intelligent integration and extrapolation of ADMET data 3. ADMET Diagnosis models Bernard Faller, Suzanne Skolnik and Jianling Wang 4. PATH (Probe ADME and Test Hypotheses): A useful approach enabling hypothesis–driven ADME optimization 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 Urban Fagerholm 6. Maximizing the power of a local model for ADMET–property prediction Sebastien Ronseaux and Jeremy Beck and Clayton Springer 7. Chemoinformatic and chemogenomic approach to ADMET Virginie Y. Martiny, Ilza Pajeva, Michael Wiese, Andrew M. Davis, Maria A. Miteva 8. Multi–Parameter Optimization of ADMET for Drug Design Matthew D. Segall and Edmund J. Champness 9. PBPK: Integrating in vitro and in silico data in physiologically based models Hannah M Jones, Neil Parrott 10. Emerging full mechanistic physiologically based modeling Kiyohiko Sugano 11. Pharmacokinetic/Pharmacodynamic modeling in drug discovery: A translational tool to optimize discovery compounds towards the ideal target–specific profile Patricia Schroeder Part III: Assessment and mitigation of critical clinically–relevant ADMET risks in drug discovery 12. In vitro – in silico tools to predict pharmacokinetics of poorly soluble drug compounds 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 Donna A. Volpe, Hong Shen, Praveen V. Balimane 14. Integrated Assessment of Drug Clearance and Cross Species Scalability 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 Tycho Heimbach, Rakesh Gollen, Handan He 16. Management and mitigation of human drug–drug interaction risks in drug discovery and development phases Heidi J. Einolf and Imad Hanna 17. Integrated Assessment and Clinical Translation of in vitro Off–target Safety Pharmacology Risks Patrick Y Muller, Christian F Trendelenburg 18. Integrated Risk Assessment of Cardiovascular Safety in Drug Discovery Gül Erdemli and Ruth L. Martin 19. Drug–induced Hepatotoxicity: Advances in Preclinical Predictive Strategies and Tools Donna M. Dambach 20. Carcinogenicity and teratogenicity assessment Hans–Jörg Martus, David Beckman, Lutz Mueller 21.. Nephrotoxicity: Development of biomarkers for preclinical and clinical application Frank Dieterle & Estelle Marrer Part IV: Success stories and Lessons learned 22.Early Intervention with Formulation Strategies for Multi–dimensional Problems to Optimize for Success Stephanie Dodd, Christina Capacci–Daniel, Chris Towler, Riccardo Panicucci, Keith Hoffmaster 23. Cytochrome P450–mediated Drug Interaction and Cardiovascular Safety: The Seldane to Allegra Transformation F. Peter Guengerich 24. Clinical toxicity profile of VEGF inhibitors M.P.S. Sie and Ferry A.L.M. Eskens 25. Cardiomyopathy: drug–induced and predisposed Shirley A. Aguirre & Eileen R. Blasi 26. Safety Management by Pharmacokinetic Considerations: Ranibizumab (Lucentis) and Bevacizumab (Avastin) Nicole H Siegel and Manju L Subramanian
- ISBN: 978-1-118-29992-0
- Editorial: Wiley–Blackwell
- Encuadernacion: Cartoné
- Páginas: 610
- Fecha Publicación: 11/04/2014
- Nº Volúmenes: 1
- Idioma: Inglés