Basic Pharmacokinetics and Pharmacodynamics: An Integrated Textbook and Computer Simulations

588 Pages·2016·21.43 MB·English

by  Sara E. Rosenbaum

90 EDITED BY
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BASIC PHARMACOKINETICS
AND PHARMACODYNAMICS

BASIC PHARMACOKINETICS
AND PHARMACODYNAMICS
An Integrated Textbook and
Computer Simulations
Second Edition
Editedby
SARAE.ROSENBAUM
Copyright©2017byJohnWiley&Sons,Inc.Allrightsreserved.
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LibraryofCongressCataloging-in-PublicationData:
Names:Rosenbaum,Sara(SaraE.),author,editor.
Title:Basicpharmacokineticsandpharmacodynamics:anintegratedtextbookandcomputersimulations/edited
bySaraE.Rosenbaum.
Description:Secondedition.|Hoboken,NewJersey:JohnWiley&Sons,Inc.,[2017]|Includesbibliographical
referencesandindex.
Identifiers:LCCN2016031846(print)|LCCN2016034126(ebook)|ISBN9781119143154(pbk.)|
ISBN9781119143161(pdf)|ISBN9781119143185(epub)
Subjects:|MESH:Pharmacokinetics|PharmacologicalPhenomena|ComputerSimulation
Classification:LCCRM301.5(print)|LCCRM301.5(ebook)|NLMQV38|DDC615/.7–dc23
LCrecordavailableathttps://lccn.loc.gov/2016031846
PrintedintheUnitedStatesofAmerica
10 9 8 7 6 5 4 3 2 1
ToSteve,MollyandLucy

CONTENTS
Preface xix
Contributors xxi
1 IntroductiontoPharmacokineticsandPharmacodynamics 1
SaraE.Rosenbaum
1.1 Introduction:DrugsandDoses, 2
1.2 IntroductiontoPharmacodynamics, 3
1.2.1 DrugEffectsattheSiteofAction, 3
1.2.2 Agonists,Antagonists,andConcentration–Response
Relationships, 6
1.3 IntroductiontoPharmacokinetics, 9
1.3.1 PlasmaConcentrationofDrugs, 9
1.3.2 ProcessesinPharmacokinetics, 11
1.4 Dose–ResponseRelationships, 12
1.5 TherapeuticRange, 14
1.5.1 DeterminationoftheTherapeuticRange, 15
1.6 Summary, 18
Reference, 18
2 PassageofDrugsThroughMembranes 19
SaraE.Rosenbaum
2.1 Introduction, 20
2.2 StructureandPropertiesofMembranes, 20
2.3 PassiveDiffusion, 21
2.3.1 TranscellularPassiveDiffusion, 23
2.3.2 ParacellularPassiveDiffusion, 25
2.4 Carrier-MediatedProcesses:TransportProteins, 26
2.4.1 UptakeTransporters:SLCSuperfamily, 27
vii
viii CONTENTS
2.4.2 EffluxTransporters:ABCSuperfamily, 29
2.4.3 CharacteristicsofTransporterSystems, 31
2.4.4 SimulationExercise, 32
2.4.5 ClinicalExamplesofTransporterInvolvementinDrug
Response, 32
References, 33
3 DrugAdministrationandDrugAbsorption 35
StevenC.Sutton
3.1 Introduction:LocalandSystemicDrugAdministration, 36
3.2 RoutesofDrugAdministration, 37
3.2.1 CommonRoutesofLocalDrugAdministration, 37
3.2.2 CommonRoutesofSystemicDrugAdministration, 38
3.3 OverviewofOralAbsorption, 41
3.3.1 AnatomyandPhysiologyoftheOral-Gastric-IntestinalTract
andTransitTime, 41
3.4 ExtentofDrugAbsorption, 44
3.4.1 BioavailabilityFactor, 44
3.4.2 IndividualBioavailabilityFactors, 45
3.5 DeterminantsoftheFractionoftheDoseAbsorbed(F), 46
3.5.1 Disintegration, 46
3.5.2 Dissolution, 46
3.5.3 FormulationExcipients, 50
3.5.4 AdverseEventswithintheGastrointestinalLumen, 50
3.5.5 TranscellularPassiveDiffusion, 53
3.5.6 ParticulateUptake, 53
3.5.7 ParacellularPassiveDiffusion, 53
3.5.8 UptakeandEffluxTransporters, 54
3.5.9 PresystemicIntestinalMetabolismorExtraction, 58
3.5.10 PresystemicHepaticMetabolismorExtraction, 60
3.6 FactorsControllingtheRateofDrugAbsorption, 61
3.6.1 Dissolution-ControlledAbsorption, 63
3.6.2 MembranePenetration-ControlledAbsorption, 63
3.6.3 OverallRateofDrugAbsorption, 63
3.7 BiopharmaceuticsClassificationSystem, 64
3.7.1 IntestinalReserveLength, 64
3.7.2 BiopharmaceuticsClassificationSystem(BCS), 64
3.7.3 BiopharmaceuticsDrugDispositionClassificationSystem
(BDDCS), 65
3.8 FoodEffects, 65
Problems, 66
References, 67
4 DrugDistribution 71
SaraE.Rosenbaum
4.1 Introduction, 72
4.2 ExtentofDrugDistribution, 72
4.2.1 DistributionVolumes, 74