Blood-Brain Barrier in Drug Discovery
Optimizing Brain Exposure of CNS Drugs and Minimizing Brain Side Effects for Peripheral Drugs
Herausgegeben von Di, Li; Kerns, Edward H.
Blood-Brain Barrier in Drug Discovery
Optimizing Brain Exposure of CNS Drugs and Minimizing Brain Side Effects for Peripheral Drugs
Herausgegeben von Di, Li; Kerns, Edward H.
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- Produkterinnerung
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…mehr
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- 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
- Produktdetails
- Verlag: Wiley & Sons
- 1. Auflage
- Seitenzahl: 608
- Erscheinungstermin: 9. Februar 2015
- Englisch
- Abmessung: 240mm x 161mm x 37mm
- Gewicht: 666g
- ISBN-13: 9781118788356
- ISBN-10: 1118788354
- Artikelnr.: 41415839
- Verlag: Wiley & Sons
- 1. Auflage
- Seitenzahl: 608
- Erscheinungstermin: 9. Februar 2015
- Englisch
- Abmessung: 240mm x 161mm x 37mm
- Gewicht: 666g
- ISBN-13: 9781118788356
- ISBN-10: 1118788354
- Artikelnr.: 41415839
H. Kerns Part 1 Pharmacokinetics of Brain Exposure 5 2 Pharmacokinetics of
CNS Penetration 7 Andreas Reichel 3 Free Drug Hypothesis for CNS Drug
Candidates 42 Xingrong Liu and Cuiping Chen 4 Species Differences and
Impact of Disease State on BBB_66 Jean-Marie Nicolas Part 2 Mechanisms of
Drugs Across the Blood-Brain Barrier 95 5 Passive Diffusion Permeability of
the BBB--Examples and SAR_97 Scott Summerfield, Phil Jeffrey, Jasminder
Sahi, and Liangfu Chen 6 Establishment of P-Glycoprotein
Structure-Transport Relationships to Optimize CNS Exposure in Drug
Discovery 113 Jerome H. Hochman, Sookhee N. Ha, and Robert P. Sheridan 7
Uptake Transport at the BBB--Examples and SAR_125 Ziqiang Cheng and Qian
Liu 8 Transport of Protein and Antibody Therapeutics across the Blood-Brain
Barrier 146 William M. Pardridge Part 3 Predicting and Measuring Brain
Exposure of Drugs 167 9 In Silico Tools for Predicting Brain Exposure of
Drugs 169 Hongming Chen, Susanne Winiwarter, and Ola Engkvist 10 In Vitro
Assays for Assessing BBB Permeability: Artificial Membrane and Cell Culture
Models 188 Alex Avdeef, Mária A. Deli, and Winfried Neuhaus 11 Human-Based
In Vitro Brain Endothelial Cell Models 238 Hannah K. Wilson and Eric V.
Shusta 12 Methods for Assessing Brain Binding 274 Li Di and Cheng Chang 13
In Vivo Studies of Brain Exposure in Drug Discovery 284 Edward H. Kerns 14
PBPK Modeling Approach for Predictions of Human CNS Drug Brain Distribution
296 Elizabeth C.M. de Lange 15 PK/PD Modeling of CNS Drug Candidates 324
Johan Gabrielsson, Stephan Hjorth, and Lambertus A. Peletier 16
Microdialysis to Assess Free Drug Concentration in Brain 351 William
Kielbasa and Robert E. Stratford, Jr. 17 Imaging Techniques for Central
Nervous System (CNS) Drug Discovery 365 Lei Zhang and Anabella Villalobos
Part 4 Modulating Brain Penetration of Leads During Drug Discovery 385 18
Designing CNS Drugs for Optimal Brain Exposure 387 Zoran Rankovic 19 Case
Studies of CNS Drug Optimization--Medicinal Chemistry and CNS Biology
Perspectives 425 Kevin J. Hodgetts 20 Designing Peripheral Drugs for
Minimal Brain Exposure 446 Peter Bungay, Sharan Bagal, and Andy Pike 21
Case Studies of Non-CNS Drugs to Minimize Brain Penetration--Nonsedative
Antihistamines 463 Andrew Crowe Part 5 Case Studies in CNS Drug Discovery
483 22 Case Study 1: The Discovery and Development of Perampanel 485
Antonio Laurenza, Jim Ferry, Haichen Yang, Shigeki Hibi, Takahisa Hanada,
and Andrew Satlin 23 Case Study 2: The Discovery and Development of the
Multimodal Acting Antidepressant Vortioxetine 505 Christoffer Bundgaard,
Alan L. Pehrson, Connie Sánchez, and Benny Bang-Andersen Part 6 Drug
Delivery Techniques to CNS 521 24 Brain Delivery Using Nanotechnology 523
Huile Gao and Xinguo Jiang 25 Intranasal Delivery to the Central Nervous
System 535 Lisbeth Illum Part 7 Future Prospects in Blood-Brain Barrier
UNDERSTANDING AND DRUG DISCOVERY 567 26 Future Perspectives 569 N. Joan
Abbott Index 580
H. Kerns Part 1 Pharmacokinetics of Brain Exposure 5 2 Pharmacokinetics of
CNS Penetration 7 Andreas Reichel 3 Free Drug Hypothesis for CNS Drug
Candidates 42 Xingrong Liu and Cuiping Chen 4 Species Differences and
Impact of Disease State on BBB_66 Jean-Marie Nicolas Part 2 Mechanisms of
Drugs Across the Blood-Brain Barrier 95 5 Passive Diffusion Permeability of
the BBB--Examples and SAR_97 Scott Summerfield, Phil Jeffrey, Jasminder
Sahi, and Liangfu Chen 6 Establishment of P-Glycoprotein
Structure-Transport Relationships to Optimize CNS Exposure in Drug
Discovery 113 Jerome H. Hochman, Sookhee N. Ha, and Robert P. Sheridan 7
Uptake Transport at the BBB--Examples and SAR_125 Ziqiang Cheng and Qian
Liu 8 Transport of Protein and Antibody Therapeutics across the Blood-Brain
Barrier 146 William M. Pardridge Part 3 Predicting and Measuring Brain
Exposure of Drugs 167 9 In Silico Tools for Predicting Brain Exposure of
Drugs 169 Hongming Chen, Susanne Winiwarter, and Ola Engkvist 10 In Vitro
Assays for Assessing BBB Permeability: Artificial Membrane and Cell Culture
Models 188 Alex Avdeef, Mária A. Deli, and Winfried Neuhaus 11 Human-Based
In Vitro Brain Endothelial Cell Models 238 Hannah K. Wilson and Eric V.
Shusta 12 Methods for Assessing Brain Binding 274 Li Di and Cheng Chang 13
In Vivo Studies of Brain Exposure in Drug Discovery 284 Edward H. Kerns 14
PBPK Modeling Approach for Predictions of Human CNS Drug Brain Distribution
296 Elizabeth C.M. de Lange 15 PK/PD Modeling of CNS Drug Candidates 324
Johan Gabrielsson, Stephan Hjorth, and Lambertus A. Peletier 16
Microdialysis to Assess Free Drug Concentration in Brain 351 William
Kielbasa and Robert E. Stratford, Jr. 17 Imaging Techniques for Central
Nervous System (CNS) Drug Discovery 365 Lei Zhang and Anabella Villalobos
Part 4 Modulating Brain Penetration of Leads During Drug Discovery 385 18
Designing CNS Drugs for Optimal Brain Exposure 387 Zoran Rankovic 19 Case
Studies of CNS Drug Optimization--Medicinal Chemistry and CNS Biology
Perspectives 425 Kevin J. Hodgetts 20 Designing Peripheral Drugs for
Minimal Brain Exposure 446 Peter Bungay, Sharan Bagal, and Andy Pike 21
Case Studies of Non-CNS Drugs to Minimize Brain Penetration--Nonsedative
Antihistamines 463 Andrew Crowe Part 5 Case Studies in CNS Drug Discovery
483 22 Case Study 1: The Discovery and Development of Perampanel 485
Antonio Laurenza, Jim Ferry, Haichen Yang, Shigeki Hibi, Takahisa Hanada,
and Andrew Satlin 23 Case Study 2: The Discovery and Development of the
Multimodal Acting Antidepressant Vortioxetine 505 Christoffer Bundgaard,
Alan L. Pehrson, Connie Sánchez, and Benny Bang-Andersen Part 6 Drug
Delivery Techniques to CNS 521 24 Brain Delivery Using Nanotechnology 523
Huile Gao and Xinguo Jiang 25 Intranasal Delivery to the Central Nervous
System 535 Lisbeth Illum Part 7 Future Prospects in Blood-Brain Barrier
UNDERSTANDING AND DRUG DISCOVERY 567 26 Future Perspectives 569 N. Joan
Abbott Index 580