Drug transporters. Volume 1, Role and importance in ADME and drug development

494 Pages·2016·7.918 MB·English

by  Glynis Nicholls, Glynis Nicholls, Kuresh Youdim, David Thurston, David Fox, John Keogh, Bruno Stieger, Bente Steffansen, Git W. Chung, David Dickens, Lena Gustavsson, Pradeep Sharma, Nico Scheer, Varma Manthena, Silke Simon, Susan Cole, Nick Plant, Aki Heikkinen, Karelle Menochet, Ichiro Leiri, David Marcus

Drug Transporters
Volume 1: Role and Importance in ADME and Drug Development
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RSC Drug Discovery Series
Editor-in-chief
Professor David Thurston, King’s College, London, UK
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93- Professor David Rotella, Montclair State University, USA
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23 Professor Ana Martinez, Centro de Investigaciones Biologicas-CSIC, Madrid,
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82 Spain
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81 Dr David Fox, Vulpine Science and Learning, UK
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or Titles in the Series:
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s.rs 1: Metabolism, Pharmacokinetics and Toxicity of Functional Groups
ub 2: Emerging Drugs and Targets for Alzheimer’s Disease; Volume 1
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p:// 3: Emerging Drugs and Targets for Alzheimer’s Disease; Volume 2
htt 4: Accounts in Drug Discovery
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01 6: Animal Models for Neurodegenerative Disease
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14: Neglected Diseases and Drug Discovery
15: Biomedical Imaging
16: Pharmaceutical Salts and Cocrystals
17: Polyamine Drug Discovery
18: Proteinases as Drug Targets
19: Kinase Drug Discovery
20: Drug Design Strategies: Computational Techniques and Applications
21: Designing Multi-Target Drugs
22: Nanostructured Biomaterials for Overcoming Biological Barriers
23: Physico-Chemical and Computational Approaches to Drug Discovery
24: Biomarkers for Traumatic Brain Injury
25: Drug Discovery from Natural Products
26: Anti-Inflammatory Drug Discovery
27: New Therapeutic Strategies for Type 2 Diabetes: Small Molecules
28: Drug Discovery for Psychiatric Disorders
29: Organic Chemistry of Drug Degradation
30: Computational Approaches to Nuclear Receptors
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31: Traditional Chinese Medicine
32: Successful Strategies for the Discovery of Antiviral Drugs
33: Comprehensive Biomarker Discovery and Validation for Clinical
Application
34: Emerging Drugs and Targets for Parkinson’s Disease
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Drug Transporters
Volume 1: Role and Importance in ADME
and Drug Development
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78 Edited by
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39/ Glynis Nicholls
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0. Independent Consultant, Wem, Shropshire, UK
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c.or Kuresh Youdim
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0. RSCDrugDiscoverySeriesNo.54
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g | PrintISBN:978-1-78262-069-3
or TwovolumesetprintISBN:978-1-78262-867-5
sc. PDFeISBN:978-1-78262-379-3
bs.r EPUBeISBN:978-1-78262-868-2
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n htt AcataloguerecordforthisbookisavailablefromtheBritishLibrary
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01 rTheRoyalSocietyofChemistry2016
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1 Apartfromfairdealingforthepurposesofresearchfornon-commercialpurposesorfor
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o privatestudy,criticismorreview,aspermittedundertheCopyright,DesignsandPatents
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e Act1988andtheCopyrightandRelatedRightsRegulations2003,thispublicationmaynot
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blis bereproduced,storedortransmitted,inanyformorbyanymeans,withouttheprior
u permissioninwritingofTheRoyalSocietyofChemistryorthecopyrightowner,orinthe
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caseofreproductioninaccordancewiththetermsoflicencesissuedbytheCopyright
LicensingAgencyintheUK,orinaccordancewiththetermsofthelicencesissuedby
theappropriateReproductionRightsOrganizationoutsidetheUK.Enquiriesconcerning
reproductionoutsidethetermsstatedhereshouldbesenttoTheRoyalSocietyof
Chemistryattheaddressprintedonthispage.
TheRSCisnotresponsibleforindividualopinionsexpressedinthiswork.
Theauthorshavesoughttolocateownersofallreproducedmaterialnotintheirown
possessionandtrustthatnocopyrightshavebeeninadvertentlyinfringed.
PublishedbyTheRoyalSocietyofChemistry,
ThomasGrahamHouse,SciencePark,MiltonRoad,
CambridgeCB40WF,UK
RegisteredCharityNumber207890
Forfurtherinformationseeourwebsiteatwww.rsc.org
PrintedintheUnitedKingdombyCPIGroup(UK)Ltd,Croydon,CR04YY,UK
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3- Preface
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10. The original aim of this book was to produce a useable handbook on drug
oi: transporters, one that would be in the offices and laboratories of scientists
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g | from every discipline as a source of reference, be it on the fundamental
or
c. aspects, or some of the newer, emerging disciplines of transporter science.
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s.r To date, there are no books that specifically address this aspect, concen-
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p tratinginsteadonin-depthreviewsanddiscussionsofparticulartopics.We
http:// hope that this book, divided into two volumes, will fill the current gap by
n encompassing a review of the available knowledge, techniques and tools
o
6 within the transporter sciences as they relate to drug disposition and
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2 pharmacokinetics. It brings together the collective knowledge of over 200
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gu yearsofexpertisefromanetworkofscientistsfromavarietyofbackgrounds
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A and countries, with a particular focus being given to the role of membrane
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n 1 transporters in drug absorption, distribution, metabolism and elimination
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d (ADME),andtheirimpactondrugsafetyanddrugefficacy.Sincethebookis
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sh intendedforbothnewcomersandestablishedscientists,coverageisgivento
ubli almostallareasofthefield,togetherwithlinkstodatabases,referencesand
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reviews for the interested reader.
For ease of reference, the book as a whole is divided into four sections,
witheachsectiondescribingthecurrent(2016)situationinthefieldofdrug
transporters. Given the extensive nature of the topics chosen, and our wish
toincludeasmanysubjectareasaspossible,ithasbeennecessarytodivide
the book into two separate volumes, with the first volume concentrating
primarily on the theory and practice of those drug transporters currently
used within the pharmaceutical industry and the second volume outlining
someoftheemergingareaswithinthefield.However,itisintendedthatthe
two volumes should, where possible, be retained together for reference
purposesandouruseoftheterm‘book’willgenerallyrefertobothvolumes.
Inthefirstvolume,DrugTransporters:Volume1RoleandImportanceinADME
RSCDrugDiscoverySeriesNo.54
DrugTransporters:Volume1:RoleandImportanceinADMEandDrugDevelopment
EditedbyGlynisNichollsandKureshYoudim
rTheRoyalSocietyofChemistry2016
PublishedbytheRoyalSocietyofChemistry,www.rsc.org
vii
View Online
viii Preface
and Drug Development, some of the basic concepts are introduced in the
initialchapter,withsubsequentchaptersfocusingonthekey ADME organs
(liver, gastrointestinal tract, kidney, blood–brain barrier and lung) and how
thedifferentialexpressionofamultitudeofcharacterizeddrugtransporters
can impact the fate of both endogenous and exogenous compounds within
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0 the human body. The following two sections cover preclinical models (in
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3- silico, in vitro and in vivo), and modelling approaches used within the
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7 pharmaceuticalindustryandhowthesecanbevaluabletoolsindetermining
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6 the importance and clinical impact of transporter mediated drug–drug
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7 interactions.Thecurrentregulatoryguidanceisalsodiscussedinthecontext
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7 of transporters and their potential clinical impact. The second volume
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39/ Drug Transporters: Volume 2: Recent Advances and Emerging Technologies, is
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0.1 dedicated to ourfinal section onemerging transporterscience, introducing
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oi: some of the newer areas and technologies where research is ongoing but is
d
g | notnecessarilypartofroutineinvestigations.Topicsrangefromfactorsthat
or may impact transporter form and function (regulation of expression,
c.
s.rs enzyme–transporter interplay and pharmacogenomics) through to more
ub practicalapproachestoimproveourunderstandingoftransporter–mediated
p
p:// interactions (using microfluidics, proteomics, in vivo imaging and
htt bioinformatics/cheminformatics). Transporters in other organs and tissues
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6 o ofthebody,notcoveredinDrugTransporters:Volume1:RoleandImportance
1
0 in ADME and Drug Development, are also briefly discussed. This section
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st servestoillustratenotonlyhowthetransporterfieldisprogressinginmany
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u different areas, but also how our knowledge is still incomplete, with much
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6 still to be done.
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on Incompletingouroriginalaim,itwasclearthatabooksuchasthiscould
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e only be achieved through collaboration—from the initialideas and support
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bli of the Royal Society of Chemistry and the Drug Metabolism Discussion
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P Group (DMDG), through to the cooperation and efforts of a total of 61
authors who are experts in their fields, drawn from industry, academia,
commercial laboratories and regulatory authorities in Europe, the USA and
Asia. The involvement and continued commitment to this book from all of
ourcollaboratorswasoutstanding,especiallygiventheirongoingworkloads,
and we remain indebted to them. Mention should also be made of our
steering team of scientists, for their invaluable input into formulating the
overall book outline, and to our panel of external reviewers, whose input
helpedtoensurethatthescientificcontentofthebookwasaccurateandup
to date.
Given the many months dedicated to this work by such an extensive
network of expert scientists, we sincerely hope that this translates into a
book that will be used by many people in the coming years as a valuable
source of reference.
Glynis Nicholls
Kuresh Youdim
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10. The editors would like to thank the following people for their input into
oi: reviewing the chapters of both volumes of this book:
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c. Drug Transporters: Volume 1: Role and Importance in ADME and Drug
s
s.r Development
b
u
p Members of the steering team and DMDG: Dr Peter Kilford (DMDG
http:// Committee/Covance Ltd), Dr Mohammed Ullah (Roche), John Keogh (JPK
n Consulting), Dr Pradeep Sharma (AstraZeneca), Dr Silke Simon (Roche),
o
6 Susan Cole (MHRA) and Dr Mohammed Atari (Cyprotex), for their helpful
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2 input and independent review of several chapters.
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gu Prof. Bruno Hagenbuch (University of Kansas) and Dr Bruno Stieger
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A (University Hospital, Zurich) for their review of Chapter 7.
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n 1 Dr Michael Gertz (Roche) for his review of Chapter 9.
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d Dr Agn`es Poirier (Roche) for her review of Chapter 10.
e
sh Dr Terry Shepard and Dr DavidWright (MHRA), and Dr Eva GilBerglund
ubli (MPA) for their review of Chapter 11.
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Drug Transporters: Volume 2: Recent Advances and Emerging Technologies
Prof. Per Artursson and Dr Fabienne Gaugaz (Uppsala University) for their
review of Chapter 3.
DrP¨arNordellandDrConstanzeHilgendorf(AstraZeneca)fortheirreview
of Chapter 4.
Dr Jose Ulloa (Bioxydyn Ltd) for his review of Chapter 6.
Dr Marco Berrera (Roche) for his review of Chapter 7.
RSCDrugDiscoverySeriesNo.54
DrugTransporters:Volume1:RoleandImportanceinADMEandDrugDevelopment
EditedbyGlynisNichollsandKureshYoudim
rTheRoyalSocietyofChemistry2016
PublishedbytheRoyalSocietyofChemistry,www.rsc.org
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3- Abbreviations
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0. ABC Adenosine triphosphate (ATP)-binding cassette transporter
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oi: (gene superfamily)
d
g | ABCB ATP-binding cassette gene subfamily B
or
c. ABCB1 Gene encoding MDR1 or P-gp
s
s.r ABCB11 Gene encoding BSEP
b
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p ABCC ATP-binding cassette gene subfamily C
p:// ABCC2 Gene encoding MRP2
htt
n ABCG ATP-binding cassette gene subfamily G
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6 ABCG2 Gene encoding BCRP
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2 ADE Absorption, distribution and elimination
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u ADME Absorption, distribution, metabolism and elimination
g
u
A ADMET Absorption, distribution, metabolism, elimination and
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1 toxicity
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d o ADR Adverse drug reaction
e
h AhR Aryl hydrocarbon receptor
s
ubli AMP Adenosine monophosphate
P
API Active pharmaceutical ingredient
ARNT Aryl hydrocarbon nuclear translocator
ASBT Apical sodium dependent bile acid transporter
ATP Adenosine triphosphate
AUC Area under curve
AUMC Area under the first order moment curve
BA Bioavailability
BBB Blood–brain barrier
BCRP Breast cancer resistance protein (gene ABCG2)
BCS Biopharmaceutics classification system
BCSFB Blood–cerebrospinal fluid barrier
BDDCS Biopharmaceutics drug disposition classification system
RSCDrugDiscoverySeriesNo.54
DrugTransporters:Volume1:RoleandImportanceinADMEandDrugDevelopment
EditedbyGlynisNichollsandKureshYoudim
rTheRoyalSocietyofChemistry2016
PublishedbytheRoyalSocietyofChemistry,www.rsc.org
x