Blood-Brain Barrier in Drug Discovery

Li Di 지음

Wiley 2014년 12월 29일 출간

작품소개

책소개

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 mostsignificant ~ and most challenging ~ areas of drugdiscovery.#8226;Written by world experts to provide practicalsolutions to increase brain penetration or minimize CNSside-effects#8226;Reviews state-of-the-art in silico, in vitro, and invivo tools to assess brain penetration and advanced CNS drugdelivery strategies#8226;Covers BBB physiology, medicinal chemistry designprinciples, free drug hypothesis for the BBB, and transportmechanisms including passive diffusion, uptake/efflux transporters,and receptor-mediated processes#8226;Highlights the advances in modelling BBBpharmacokinetics and dynamics relationships (PK/PD) andphysiologically-based pharmacokinetics (PBPK)#8226;Discusses case studies of successful CNS and non-CNSdrugs, lessons learned and paths to the market

목차

Contributors ixPreface xiii1 Introduction and Overview 1Li Di and Edward H. KernsPart 1 Pharmacokinetics of Brain Exposure 52 Pharmacokinetics of CNS Penetration 7Andreas Reichel3 Free Drug Hypothesis for CNS Drug Candidates 42Xingrong Liu and Cuiping Chen4 Species Differences and Impact of Disease State onBBB_66Jean-Marie NicolasPart 2 Mechanisms of Drugs Across the Blood&~BrainBarrier 955 Passive Diffusion Permeability of the BBB&-Examples andSAR_97Scott Summerfield, Phil Jeffrey, Jasminder Sahi, and LiangfuChen6 Establishment of P-Glycoprotein Structure&~TransportRelationships to Optimize CNS Exposure in Drug Discovery 113Jerome H. Hochman, Sookhee N. Ha, and Robert P. Sheridan7 Uptake Transport at the BBB&-Examples and SAR_125Ziqiang Cheng and Qian Liu8 Transport of Protein and Antibody Therapeutics across theBlood&~Brain Barrier 146William M. PardridgePart 3 Predicting and Measuring Brain Exposure of Drugs1679 In Silico Tools for Predicting Brain Exposure of Drugs169Hongming Chen, Susanne Winiwarter, and Ola Engkvist10 In Vitro Assays for Assessing BBB Permeability: ArtificialMembrane and Cell Culture Models 188Alex Avdeef, Mária A. Deli, and Winfried Neuhaus11 Human-Based In Vitro Brain Endothelial Cell Models 238Hannah K. Wilson and Eric V. Shusta12 Methods for Assessing Brain Binding 274Li Di and Cheng Chang13 In Vivo Studies of Brain Exposure in Drug Discovery 284Edward H. Kerns14 PBPK Modeling Approach for Predictions of Human CNS DrugBrain Distribution 296Elizabeth C.M. de Lange15 PK/PD Modeling of CNS Drug Candidates 324Johan Gabrielsson, Stephan Hjorth, and Lambertus A.Peletier<

작가정보

저자(글) Li Di

Li Di is an associate research fellow in the Pharmacokinetics, Dynamics, and Drug Metabolism Department at Pfizer Global Research and Development and has extensive experience in the pharmaceutical industry. She has over 100 publications, presented over 70 invited lectures, and teaches an American Chemical Society short course on drug-like properties.Edward Kerns worked in pharmaceutical research and development for over 30 years, was associate director at Wyeth and Bristol-Myers Squibb, then was at the NIH-National Center for Advancing Translational Sciences. He published over 90 journal papers or book chapters and 3 books, and teaches an American Chemical Society short course on drug-like properties.