The landmark textbook on the theoretical and practical applications of biopharmaceutics and pharmacokinetics-now fully updated.

1. Introduction to Biopharmaceutics and PharmacokineticsDrug Product PerformanceBiopharmaceuticsPharmacokineticsPharmacodynamicsClinical PharmacokineticsPractical FocusPharmacodynamicsDrug Exposure and Drug ResponseToxicokinetics and Clinical ToxicologyMeasurement of Drug ConcentrationsBasic Pharmacokinetics and Pharmacokinetic ModelsChapter SummaryLearning QuestionsAnswersReferencesBibliography2. Mathematical Fundamentals in PharmacokineticsCalculusGraphsPractice ProblemMathematical Expressions and UnitsUnits for Expressing Blood ConcentrationsMeasurement and Use of Significant FiguresPractice ProblemPractice ProblemRates and Orders of ProcessesChapter SummaryLearning QuestionsAnswersReferences3. BiostatisticsVariablesTypes of Data (Nonparametric Versus Parametric)DistributionsMeasures of Central TendencyMeasures of VariabilityHypothesis TestingStatistically Versus Clinically Significant DifferencesStatistical Inference Techniques in Hypothesis Testing for Parametric DataGoodness of FitStatistical Inference Techniques for Hypothesis Testing With Nonparametric DataControlled Versus Noncontrolled StudiesBlindingConfoundingValidityBioequivalence StudiesEvaluation of Risk for Clinical StudiesChapter SummaryLearning QuestionsAnswersReferences4. One-Compartment Open Model: Intravenous Bolus AdministrationElimination Rate ConstantApparent Volume of DistributionClearanceClinical ApplicationCalculation of k From Urinary Excretion DataPractice ProblemPractice ProblemClinical ApplicationChapter SummaryLearning QuestionsAnswersReferenceBibliography5. Multicompartment Models: Intravenous Bolus AdministrationTwo-Compartment Open ModelClinical ApplicationPractice ProblemPractical FocusPractice ProblemPractical FocusThree-Compartment Open ModelClinical ApplicationClinical ApplicationDetermination of Compartment ModelsPractical FocusClinical ApplicationPractical ProblemClinical ApplicationPractical ApplicationClinical ApplicationChapter SummaryLearning QuestionsAnswersReferencesBibliography6. Intravenous InfusionOne-Compartment Model DrugsInfusion Method for Calculating Patient Elimination Half-LifeLoading Dose Plus IV Infusion-One-Compartment ModelPractice ProblemsEstimation of Drug Clearance and VD From Infusion DataIntravenous Infusion of Two-Compartment Model DrugsPractical FocusChapter SummaryLearning QuestionsAnswersReferenceBibliography7. Drug Elimination, Clearance, and Renal ClearanceDrug EliminationDrug ClearanceClearance ModelsThe KidneyClinical ApplicationPractice ProblemsRenal ClearanceDetermination of Renal ClearancePractice ProblemPractice ProblemRelationship of Clearance to Elimination Half-Life and Volume of DistributionChapter SummaryLearning QuestionsAnswersReferencesBibliography8. Pharmacokinetics of Oral AbsorptionIntroductionBasic Principles of Physiologically Based Absorption Kinetics (Bottom-Up Approach)Absoroption Kinetics (The Top-Down Approach)Pharmacokinetics of Drug AbsorptionSignificance of Absorption Rate ConstantsZero-Order Absorption ModelClinical Application-Transdermal Drug DeliveryFirst-Order Absorption ModelPractice ProblemChapter SummaryAnswersApplication QuestionsReferencesBibliography9. Multiple-Dosage RegimensDrug AccumulationClinical ExampleRepetitive Intravenous InjectionsIntermittent Intravenous InfusionClinical ExampleEstimation of k and VD of Aminoglycosides in Clinical SituationsMultiple-Oral-Dose RegimenLoading DoseDosage Regimen SchedulesClinical ExamplePractice ProblemsChapter SummaryLearning QuestionsAnswersReferencesBibliography10. Nonlinear PharmacokineticsSaturable Enzymatic Elimination ProcessesPractice ProblemPractice ProblemDrug Elimination by Capacity-Limited Pharmacokinetics: One-Compartment Model, IV Bolus InjectionPractice ProblemsClinical FocusClinical FocusDrugs Distributed as One-Compartment Model and Eliminated by Nonlinear PharmacokineticsClinical FocusChronopharmacokinetics and Time-Dependent PharmacokineticsClinical FocusBioavailability of Drugs That Follow Nonlinear PharmacokineticsNonlinear Pharmacokinetics Due to Drug-Protein BindingPotential Reasons for Unsuspected NonlinearityDose-Dependent PharmacokineticsClinical ExampleChapter SummaryLearning QuestionsAnswersReferencesBibliography11. Physiologic Drug Distribution and Protein BindingPhysiologic Factors of DistributionClinical FocusApparent Volume DistributionPractice ProblemProtein Binding of DrugsClinical ExamplesEffect of Protein Binding on the Apparent Volume of DistributionPractice ProblemClinical ExampleRelationship of Plasma Drug-Protein Binding to Distribution and EliminationClinical ExamplesClinical ExampleDeterminants of Protein BindingClinical ExampleKinetics of Protein BindingPractical FocusDetermination of Binding Constants and Binding Sites by Graphic MethodsClinical Significance of Drug-Protein BindingClinical ExampleClinical ExampleModeling Drug DistributionChapter SummaryLearning QuestionsAnswersReferencesBibliography12. Drug Elimination and Hepatic ClearanceRoute of Drug Administration and Extrahepatic Drug MetabolismPractical FocusHepatic ClearanceExtrahepatic MetabolismEnzyme Kinetics-Michaelis-Menten EquationClinical ExamplePractice ProblemAnatomy and Physiology of the LiverHepatic Enzymes Involved in the Biotransformation of DrugsDrug Biotransformation ReactionsPathways of Drug BiotransformationDrug Interaction ExampleClinical ExampleFirst-Pass EffectsHepatic Clearance of a Protein-Bound Drug: Restrictive and Nonrestrictive Clearance From BindingBiliary Excretion of DrugsClinical ExampleRole of Transporters on Hepatic Clearance and BioavailabilityChapter SummaryLearning QuestionsAnswersReferencesBibliography13. Pharmacogenetics and Drug MetabolismGenetic PolymorphismsCytochrome P-450 IsozymesPhase II EnzymesTransportersChapter SummaryGlossaryAbbreviationsReferences14. Physiologic Factors Related to Drug AbsorptionDrug Absorption and Design of a Drug ProductRoute of Drug AdministrationNature of Cell MembranesPassage of Drugs Across Cell MembranesDrug Interactions in the Gastrointestinal TractOral Drug AbsorptionOral Drug Absorption During Drug Product DevelopmentMethods for Studying Factors That Affect Drug AbsorptionEffect of Disease States on Drug AbsorptionMiscellaneous Routes of Drug AdministrationChapter SummaryLearning QuestionsAnswers to QuestionsReferencesBibliography15. Biopharmaceutic Considerations in Drug Product Design and In Vitro Drug Product PerformanceBiopharmaceutic Factors and Rationale for Drug Product DesignRate-Limiting Steps in Drug AbsorptionPhysicochemical Properties of the DrugFormulation Factors Affecting Drug Product PerformanceDrug Product Performance, In Vitro: Dissolution and Drug Release TestingCompendial Methods of DissolutionAlternative Methods of Dissolution TestingDissolution Profile ComparisonsMeeting Dissolution RequirementsProblems of Variable Control in Dissolution TestingPerformance of Drug Products: In Vitro-In Vivo CorrelationApproaches to Establish Clinically Relevant Drug Product SpecificationsDrug Product StabilityConsiderations in the Design of a Drug ProductDrug Product ConsiderationsClinical ExampleChapter SummaryLearning QuestionsAnswersReferencesBibliography16. Drug Product Performance, In Vivo: Bioavailability and BioequivalenceDrug Product PerformancePurpose of Bioavailability and Bioequivalence StudiesRelative and Absolute AvailabilityPractice ProblemMethods for Assessing Bioavailability and BioequivalenceIn Vivo Measurement of Active Moiety or Moieties in Biological FluidsBioequivalence Studies Based on Pharmacodynamic Endpoints-In Vivo Pharmacodynamic (PD) ComparisonBioequivalence Studies Based on Clinical Endpoints-Clinical Endpoint StudyIn Vitro StudiesOther Approaches Deemed Acceptable (by the FDA)Bioequivalence Studies Based on Multiple EndpointsBioequivalence StudiesDesign and Evaluation of Bioequivalence StudiesStudy DesignsCrossover Study DesignsClinical ExampleClinical ExamplePharmacokinetic Evaluation of the DataThe Partial AUC in Bioequivalence AnalysisExamples of Partial AUC AnalysesBioequivalence ExamplesStudy Submission and Drug Review ProcessWaivers of In Vivo Bioequivalence Studies (Biowaivers)The Biopharmaceutics Classification System (BCS)Generic Biologics (Biosimilar Drug Products)Clinical Significance of Bioequivalence StudiesSpecial Concerns in Bioavailability and Bioequivalence StudiesGeneric SubstitutionGlossaryChapter SummaryLearning QuestionsAnswersReferences17. Biopharmaceutical Aspects of the Active Pharmaceutical Ingredient and Pharmaceutical EquivalenceIntroductionPharmaceutical AlternativesPractice ProblemBioequivalence of Drugs With Multiple IndicationsFormulation and Manufacturing Process ChangesSize, Shape, and Other Physical Attributes of Generic Tablets and CapsulesChanges to an Approved NDA or ANDAThe Future of Pharmaceutical Equivalence and Therapeutic EquivalenceBiosimilar Drug ProductsHistorical PerspectiveChapter SummaryLearning QuestionsAnswersReferences18. Impact of Biopharmaceutics on Drug Product Quality and Clinical EfficacyRisks From MedicinesRisk AssessmentDrug Product Quality and Drug Product PerformancePharmaceutical DevelopmentExample of Quality RiskExcipient Effect on Drug Product PerformancePractical FocusQuality Control and Quality AssurancePractical FocusRisk ManagementScale-Up and Postapproval Changes (SUPAC)Practical FocusProduct Quality ProblemsPostmarketing SurveillanceGlossaryChapter SummaryLearning QuestionsAnswersReferencesBibliography19. Modified-Release Drug Products and Drug DevicesModified-Release (MR) Drug Products and Conventional (Immediate-Release, IR) Drug ProductsBiopharmaceutic FactorsDosage Form SelectionAdvantages and Disadvantages of Extended-Release ProductsKinetics of Extended-Release Dosage FormsPharmacokinetic Simulation of Extended-Release ProductsClinical ExamplesTypes of Extended-Release ProductsConsiderations in the Evaluation of Modified-Release ProductsEvaluation of Modified-Release ProductsEvaluation of In Vivo Bioavailability DataChapter SummaryLearning QuestionsReferencesBibliography20. Targeted Drug Delivery Systems and Biotechnological ProductsBiotechnologyDrug Carriers and TargetingTargeted Drug DeliveryPharmacokinetics of BiopharmaceuticalsBioequivalence of Biotechnology-Derived Drug ProductsLearning QuestionsAnswersReferencesBibliography21. Relationship Between Pharmacokinetics and PharmacodynamicsPharmacokinetics and PharmacodynamicsRelationship of Dose to Pharmacologic EffectRelationship Between Dose and Duration of Activity (teff), Single IV Bolus InjectionPractice ProblemEffect of Both Dose and Elimination Half-Life on the Duration of ActivityEffect of Elimination Half-Life on Duration of ActivitySubstance Abuse PotentialDrug Tolerance and Physical DependencyHypersensitivity and Adverse ResponseChapter SummaryLearning QuestionsAnswersReferences22. Application of Pharmacokinetics to Clinical SituationsMedication Therapy ManagementIndividualization of Drug Dosage RegimensTherapeutic Drug MonitoringClinical ExampleClinical ExampleDesign of Dosage RegimensConversion From Intravenous Infusion to Oral DosingDetermination of DosePractice ProblemsEffect of Changing Dose ond Dosing Interval on ... and ...Determination of Frequency of Drug AdministrationDetermination of Both Dose and Dosage IntervalPractice ProblemDetermination of Route of AdministrationDosing Infants and ChildrenPractice ProblemDosing the ElderlyPractice ProblemsClinical ExampleDosing the Obese PatientsPharmacokinetics of Drug InteractionsInhibition of Drug MetabolismInhibition of Monoamine Oxidase (MAO)Induction of Drug MetabolismInhibition of Drug AbsorptionInhibition of Biliary ExcretionAltered Renal Reabsorption Due to Changing Urinary pHPractical FocusEffect of Food on Drug DispositionAdverse Viral Drug InteractionsPopulation PharmacokineticsClinical ExampleRegional PharmacokineticsChapter SummaryLearning QuestionsAnswersReferencesBibliography23. Application of Pharmacokinetics to Specific Populations: Geriatric, Obese, and Pediatric PatientsSpecific and Special PopulationsModule I: Application of Pharmacokinetics to the Geriatric PatientsSummaryLearning QuestionsAnswersReferencesFurther ReadingModule II: Application of Pharmacokinetics to the Obese PatientsSummaryLearning QuestionsAnswersReferencesModule III: Application of Pharmacokinetics to the Pediatric PatientsSummaryLearning QuestionsAnswersReferences24. Dose Adjustment in Renal and Hepatic DiseaseRenal ImpairmentPharmacokinetic ConsiderationsGeneral Approaches for Dose Adjustment in Renal DiseaseMeasurement of Glomerular Filtration RateSerum Creatinine Concentration and Creatinine ClearancePractice ProblemsDose Adjustment for Uremic PatientsPractice ProblemPractice ProblemPractice ProblemsPractice ProblemExtracorporeal Removal of DrugsPractice ProblemClinical ExamplesEffect of Hepatic Disease on PharmacokineticsPractice ProblemChapter SummaryLearning QuestionsAnswersReferencesBibliography25. Empirical Models, Mechanistic Models, Statistical Moments, and Noncompartmental AnalysisEmpirical ModelsMechanistic ModelsNoncompartmental AnalysisComparison of Different ApproachesSelection of Pharmacokinetic ModelsChapter SummaryLearning QuestionsAnswersReferencesBibliographyAppendix A Applications of Software Packages in PharmacokineticsAppendix B GlossaryIndex