Blood-Brain Barrier in Drug Discovery: Optimizing Brain Exposure of CNS Drugs and Minimizing Brain Side Effects for Peripheral Drugs

Focused on central nervous system (CNS) drug discovery efforts, this book educates drug researchers about the blood–brain barrier (BBB) so they can affect important improvements in one of the most significant – and most challenging – areas of drug discovery.• Written by world experts to provide practical solutions to increase brain penetration or minimize CNS side–effects• Reviews state–of–the–art in silico, in vitro, and in vivo tools to assess brain penetration and advanced CNS drug delivery strategies• Covers BBB physiology, medicinal chemistry design principles, free drug hypothesis for the BBB, and transport mechanisms including passive diffusion, uptake/efflux transporters, and receptor–mediated processes• Highlights the advances in modelling BBB pharmacokinetics and dynamics relationships (PK/PD) and physiologically–based pharmacokinetics (PBPK)• Discusses case studies of successful CNS and non–CNS drugs, lessons learned and paths to the market INDICE: Summary List of Chapters1. Overview/IntroductionLi Di (Pfizer Inc.) and Edward H. KernsPharmacokinetics of Brain Exposure2. Pharmacokinetics of CNS penetrationAndreas Reichel (Bayer)3. Free Drug Hyposthesis for CNS Drug CandidatesXingrong Liu (Genentech)4. Species Differences and impact of desease state on BBBJean–Marie Nicolas (UCB Pharma S.A.)Mechanisms of Drugs Across the Blood–Brain Barrier5. Passive diffusion permeability of the BBB examples and SARPhil Jeffrey (GSK)6. Efflux transport at the BBB examples and SARJerome Hochman (Merck)7. Uptake transport at the BBB examples and SARZack Cheng (AstraZeneca)8. Uptake of proteins and antibodies at the BBBWilliam Pardridge (UCLA)Predicting and Measuring Brain Exposure of Drugs9. In silico tools for assessing brain exposureHongming Chen (AstraZeneca)10. In vitro assays for assessing BBB permeability vascular cells, artificial membranes, brain slice, cell uptakeWinfried Neuhaus (University of Vienna)11. Human–based in vitro endothelial cell modelsEric Shusta (University of Wisconsin)12. In vitro assays for assessing brain bindingLi Di (Pfizer)13. In vivo studies of brain exposureEdward H. Kerns14. PBPK models for BBBElizabeth de Lange (Leiden University)15. PK/PD modeling of CNS drug candidatesJohan Gabrielsson (Swedish University)16. Microdialysis to assess free drug concentration in brainWilliam Kielbasa (Lilly)17. Imaging technique for CNS drug discoveryLei Zhang (Pfizer Inc.)Modulating Brain Penetration of Leads During Drug Discovery18. Designing CNS drugs for optimal brain exposureZoran Rankovic (Lilly)19. Case studies of CNS drug optimization medicinal chemistry and CNS biology perspectivesKevin J. Hodgetts (Harvard NeuroDiscovery Center)20. Designing peripheral drugs for minimal brain exposuePeter Bungay (Pfizer)21. Case studies of non–CNS drugs to minimize brain penetration Nonsudative antihistaminesAndrew Crowe (Curtin University)Case Studies in CNS Drug Discovery22. Case study 1 on discovery of a successful CNS drug – Fycompa (AMPA Receptor Antagonist)Andrew Satlin and Antonio Laurenza (Eisai)23. Case study 2 on discovery of a successful CNS drug – Vortioxetine (Serotonin Modulator and Stimulator)Benny Bang–Andersen (Lundbeck)Drug Delivery Techniques to CNS24. Brain delivery using nanotechnologyXinguo Jiang (Fudan University)25. Intranasal delivery to CNSLisbeth Illum (University of Nottingham)Future Prospective in Blood Brain Barrier Advancement26. Conclusion RemarksJoan Abbott (King?s College)

• ISBN: 978-1-118-78835-6
• Editorial: Wiley–Blackwell
• Encuadernacion: Cartoné
• Páginas: 600
• Fecha Publicación: 06/03/2015
• Nº Volúmenes: 1
• Idioma: Inglés