Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulations. Sheila Annie Peters
rel="nofollow" href="#ulink_d58717d2-7060-5f2d-982c-d9dc17970fbb">8.5 APPLICATIONS OF PBPK MODELING OF MONOCLONAL ANTIBODIES KEYWORDS REFERENCES 9 UNCERTAINTY AND POPULATION VARIABILITY 9.1 INTRODUCTION 9.2 DISTINGUISHING UNCERTAINTY AND VARIABILITY 9.3 SOURCES OF UNCERTAINTY IN DRUG‐RELATED PARAMETERS 9.4 SOURCES OF VARIABILITY IN SYSTEM PARAMETERS 9.5 HANDLING POPULATION VARIABILITY 9.6 UNCERTAINTY AND SENSITIVITY ANALYSIS 9.7 UNCERTAINTY AND POPULATION VARIABILITY IN CLINICAL EFFICACY AND SAFETY KEYWORDS REFERENCES 10 NONCLINICAL, CLINICAL, AND MODEL‐INFORMED DRUG DEVELOPMENT 10.1 INTRODUCTION: AN OVERVIEW OF DIFFERENT PHASES OF DRUG DEVELOPMENT 10.2 NONCLINICAL DEVELOPMENT 10.3 CLINICAL PHARMACOLOGY STUDIES 10.4 CLINICAL DEVELOPMENT IN ONCOLOGY 10.5 FAST TRACK ROUTES TO ADDRESS UNMET MEDICAL NEED IN THE TREATMENT OF SERIOUS CONDITIONS 10.6 MODEL‐INFORMED DRUG DEVELOPMENT 10.7 PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELS COMPLEMENTING CLINICAL PHARMACOLOGY STUDIES 10.8 PBPK IN ONCOLOGY REGULATORY GUIDELINES REFERENCES
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SECTION II: APPLICATIONS IN THE PHARMACEUTICAL INDUSTRY
11 OVERVIEW OF PBPK APPLICATIONS
11.1 INTRODUCTION
11.2 PBPK APPLICATIONS FOR INTERNAL DECISIONS
11.3 PBPK APPLICATIONS FOR REGULATORY FILING
11.4 PBPK MODELING AND SIMULATIONS ALONG THE VALUE CHAIN
REFERENCES
12 APPLICATIONS OF HYPOTHESIS GENERATION AND TESTING WITH PBPK MODELS
12.1 INTRODUCTION
12.2 HYPOTHESIS GENERATION AND TESTING WITH PBPK MODELS
12.3 HYPOTHESIS GENERATION AND TESTING ALONG THE VALUE CHAIN
12.4 CONCLUSIONS
REFERENCES
13 APPLICATIONS OF PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELS INTEGRATED WITH DRUG EFFECT MODELS (PBPK/PD)
13.1 INTRODUCTION: INTEGRATION OF PBPK WITH DRUG EFFECT MODELS
13.2 DOSING IN SPECIFIC POPULATIONS
13.3 PBPK/PD FOR BOTTOM‐UP PREDICTION OF INTER‐PATIENT VARIABILITY IN DRUG RESPONSE
13.4 PBPK/PD FOR PREDICTING THE INTER‐PATIENT VARIABILITY IN RESPONSE TO PRODRUGS AND ACTIVE METABOLITES
13.5 PBPK/PDWHEN SYSTEMIC CONCENTRATIONS ARE NOTTHE DRIVER FOR DRUG RESPONSE
13.6 PBPK/PD FOR MONOCLONAL ANTIBODIES
13.7 PBPK MODELS LINKED TO QUANTITATIVE SYSTEMS PHARMACOLOGY AND TOXICOLOGY MODELS
13.8 CONCLUSIONS
REFERENCES
14 PBPK MODELING AND SIMULATIONS TO EVALUATE CLINICAL DRUG‐DRUG INTERACTIONS
14.1 INTRODUCTION
14.2 CLINICAL DDI STUDIES AND MODELING APPROACHES TO ADDRESS KEY QUESTIONS RELATED TO DRUG–DRUG INTERACTIONS
14.3 PBPK MODELING OF DIFFERENT TYPES OF DRUG INTERACTIONS
14.4 DDI PREDICTIONS WITH PBPK MODELING AND SIMULATIONS INCLINICAL DRUG DEVELOPMENT AND REGULATORY SUBMISSIONS
14.5 COMPARISON OF DDI PREDICTION USING STATIC AND DYNAMIC MODELS
14.6 CONCLUSIONS
REFERENCES
15 DOSE EXTRAPOLATION ACROSS POPULATIONS (HEALTHY ADULT CAUCASIAN TO PEDIATRIC, PREGNANT WOMEN, DIFFERENT ETHNICITIES, GERIATRIC, SMOKERS AND OBESE POPULATIONS)
15.1 INTRODUCTION
15.2 PBPK MODELING STRATEGY FOR DOSE EXTRAPOLATION TO SPECIFIC POPULATIONS
15.3 POTENTIAL BENEFITS OF PBPK MODELING FOR DOSE EXTRAPOLATIONS TO SPECIFIC POPULATIONS
15.4 DOSE EXTRAPOLATIONS TO SPECIFIC POPULATIONS
15.5 CONCLUSIONS
REFERENCES
16 DOSE EXTRAPOLATION ACROSS POPULATIONS: HEALTHY ADULT TO HEPATIC AND RENAL IMPAIRMENT POPULATIONS
16.1 INTRODUCTION
16.2 PATHOPHYSIOLOGICAL CHANGES IN ORGAN IMPAIRMENT
16.3 PBPK MODELING STRATEGY: MODEL DEVELOPMENT, VERIFICATION, VALIDATION, AND APPLICATION
16.4 BENEFITSOFAPPLYINGVALIDATEDPBPKMODELSTOORGAN‐IMPAIRED POPULATIONS