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Blood-brain barrier in drug discovery : optimizing brain exposure of CNS drugs and minimizing brain side effects for peripheral drugs

Author: Li Di; Edward Harvel Kerns
Publisher: Hoboken, N.J. : John Wiley & Sons Inc., [2015] ©2015
Edition/Format:   Print book : EnglishView all editions and formats
Database:WorldCat
Summary:
"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  Read more...
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Additional Physical Format: Online version:
Blood-brain barrier in drug discovery.
Hoboken, New Jersey : Wiley, [2015]
(DLC) 2014041569
(OCoLC)893389733
Document Type: Book
All Authors / Contributors: Li Di; Edward Harvel Kerns
ISBN: 9781118788356 1118788354
OCLC Number: 889736023
Description: xiv, 586 pages, 4 unnumbered pages of plates : illustrations (some color) ; 25 cm
Contents: Introduction and overview / Li Di, and Edward H. Kerns --
Part 1: Pharmacokinetics of brain exposure. Pharmacokinetics of CNS penetration / Andreas Reichel --
Free drug hypothesis for CNS drug candidates / Xingrong Liu and Cuiping Chen --
Species differences and impact of disease state on BBB / Jean-Marie Nicolas --
Part 2: Mechanisms of drugs across the blood-brain barrier. Passive diffusion permeability of the BBB: examples and SAR / Scott Summerfield, Phil Jeffrey, Jasminder Sahi, and Liangfu Chen --
Efflux transport at the BBB: examples and SAR / Jerome Hochman --
Establishment of P-glycoprotein structure-transport relationships to optimize CNS exposure in drug discovery / Jerome H. Hochman, Sookhee N. Ha, and Robert P. Sheridan --
Uptake transport at the BBB: examples and SAR / Ziquiang Cheng and Qian Liu --
Transport of protein and antibody therapeutics across the blood-brain barrier / William M. Pardridge --
Part 3: Predicting and measuring brain exposure of drugs. In silico tools for assessing brain exposure / Hongming Chen, Susanne Winiwarter, and Ola Engkvist --
In vitro assays for assessing BBB permeability: vascular cells, artificial membranes, brain slice, cell uptake / Alex Avdeef, Mária A. Deli, and Winfried Neuhaus --
Human-based in vitro endothelial cell models / Hannah K. Wilson and Eric Shusta --
Methods for assessing brain binding / Li Di and Cheng Chang --
In vivo studies of brain exposure in drug discovery / Edward H. Kerns --
PBPK modelling approach for predictions of human CNS drug brain distribution / Elizabeth C.M. de Lange --
PK/PD modeling of CNS drug candidates / Johan Gabrielsson, Stephan Hjorth, and Lambertus A. Peletier --
Microdialysis to assess free drug concentration in brain / William Kielbasa and Robert E. Stratford, Jr. --
Imaging techniques for central nervous system (CNS) drug discovery / Lei Zhang and Anabella Villalobos --
Part 4: Modulating brain penetration of leads during drug discovery. Designing CNS drugs for optimal brain exposure / Zoran Rankovic --
Case studies of CNS drug optimization: medicinal chemistry and CNS biology perspectives / Kevin J. Hodgetts --
Designing peripheral drugs for minimal brain exposure / Peter Bungay, Sharan Bagal, and Andy Pike --
Case studies of non-CNS drugs to minimize brain penetration: nonsedative antihistamines / Andrew Crowe --
Part 5: Case studies in CNS drug discovery. Case study 1: the discovery and development of perampanel / Antonio Laurenza, Jim Ferry, Haichen Yang, Shigeki Hibi, Takahisa Hanada, and Andrew Satlin --
Case study 2: the discovery and development of the multimodal acting antidepressant vortioxetine / Christoffer Bundgaard, Alan L. Pehrson, Connie Sánchez, and Benny Bang-Andersen --
Part 6: Drug delivery techniques to CNS. Brain delivery using nanotechnology / Huile Gao and Xinguo Jiang --
Intranasal delivery to the central nervous system / Lisbeth Illum --
Part 7: Future prospects in blood-brain barrier understanding and drug discovery. Future perspectives / N. Joan Abbott .
Responsibility: edited by Li Di, Pharmacokinetics, Dynamics and Metabolism, Pfizer, Inc., Groton, Connecticut, USA, Edward H. Kerns, Laytonsville, MD, USA.

Abstract:

"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"--

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