UID:
almafu_9960052284902883
Format:
1 online resource
ISBN:
9781118140291
,
111814029X
,
9781119497813
,
1119497817
Content:
Annotation
Note:
Machine generated contents note: PRINCIPLES AND METHODS --
,
Modeling In The Pharmaceutical Industry --
,
Introduction --
,
Modeling Approaches --
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Steps Needed to Maximize Effective Integration of Models into R&D Workflow --
,
Scope of the Book --
,
Keywords --
,
References --
,
Physiologically-Based Modeling --
,
Introduction --
,
Examples of Physiological Modeling --
,
Need for Physiological Models in the Pharmaceutical Industry --
,
Organs as Compartments --
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Bottom-Up vs.
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Top-Down Modeling in Pharmacokinetics --
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References --
,
Review Of Pharmacokinetic Principles --
,
Introduction --
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Routes of Administration --
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Drug Disposition --
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Absorption --
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Plasma Protein Binding, Blood-Plasma Ratio --
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Distribution, Elimination, Half-Life, and Clearance --
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Role of Transporters in ADME --
,
Linear and Nonlinear Pharmacokinetics --
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Steady-State Pharmacokinetics --
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Dose Estimations --
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Successful PK Optimization in Drug Discovery --
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Keywords --
,
References --
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Physiological Model For Absorption --
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Introduction --
,
Drug Absorption and Gut Bioavailability --
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Solubility and Dissolution Rate --
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Permeability: Transcelluar, Paracellular, and Carrier-Mediated Pathways --
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Barriers to Membrane Transport -- Luminal Degradation, Efflux, and Gut Metabolism --
,
Factors Affecting Drug Absorption and Gut Bioavailability --
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Physiological Factors Affecting Oral Drug Absorption and Species Differences in Physiology --
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Compound-Dependent Factors --
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Formulation-Dependent Factors --
,
In Silico Predictions of Passive Permeability and Solubility --
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In Silico Models for Permeability --
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In Silico Models for Solubility --
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Measurement of Permeability, Solubility, Luminal Stability, Efflux, and Intestinal Metabolism --
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In Vitro, in Situ and in Vivo Assays for Permeability --
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Measurement of Thermodynamic or Equilibrium Solubility --
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Luminal Stability --
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Efflux --
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In Vitro Models for Estimating Extent of Gut Metabolism --
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Absorption Modeling --
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Keywords --
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References --
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Physiological Model For Distribution --
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Introduction --
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Factors Affecting Tissue Distribution of Xenobiotics --
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Physiological Factors and Species Differences in Physiology --
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Compound-Dependent Factors --
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In Silico Models of Tissue Partition Coefficients --
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Measurement of Parameters Representing Rate and Extent of Tissue Distribution --
,
Assessment of Rate and Extent of Brain Penetration --
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Physiological Model for Drug Distribution --
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Drug Concentrations at Site of Action --
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Keywords --
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References --
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Physiological Models For Drug Metabolism And Excretion --
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Introduction --
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Factors Affecting Drug Metabolism and Excretion of Xenobiotics --
,
Models for Hepatobiliary Elimination and Renal Excretion --
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In Silico Models --
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In Vitro Models for Hepatic Metabolism --
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In Vitro Models for Transporters --
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Physiological Models --
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Hepatobiliary Elimination of Parent Drug and Metabolites --
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Renal Excretion --
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References --
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Generic Whole-Body Physiologically-Based Pharmacokinetic Modeling --
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Introduction --
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Structure of a Generic Whole Body PBPK Model --
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Model Assumptions --
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Commercial PBPK Software --
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References --
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Variability, Uncertainty, And Sensitivity Analysis --
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Introduction --
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Need for Uncertainty Analysis --
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Sources of Physiological, Anatomical, Enzymatic, and Transporter Variability --
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Modeling Uncertainty and Population Variability with Monte Carlo Simulations --
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Sensitivity Analysis --
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Conclusions --
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Keywords --
,
References --
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Evaluation Of Drug-Drug Interaction Risk With Pbpk Models --
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Introduction --
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Factors Affecting Drug -- Drug Interactions --
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In Vitro Methods to Evaluate Drug -- Drug Interactions --
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Candidate Drug as a Potential Inhibitor --
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Candidate Drug as a Potential Victim of Inhibition --
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Static Models to Evaluate Drug -- Drug Interactions --
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PBPK Models to Evaluate Drug -- Drug Interactions --
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Intrinsic Clearance of Victim (V) in the Absence of Inhibitor or Inducer --
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Intrinsic Clearance of Victim (V) in the Presence of Inhibitor --
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Time-Dependent Changes in the Abundance of an Enzyme Isoform Inhibited by an MBI --
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Intrinsic Clearance of Victim (V) in the Presence of Inducer --
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Comparison of PBPK Models and Static Models for the Evaluation of Drug -- Drug Interactions --
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Keywords --
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References --
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Physiologically-Based Pharmacokinetics Of Biotherapeutics --
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Introduction --
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Therapeutic Proteins --
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Peptides and Proteins --
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Monoclonal Antibodies --
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Pharmacokinetics of Therapeutic Proteins --
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Peptides and Proteins --
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Monoclonal Antibodies --
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PBPK/PD Modeling for Therapeutic Proteins --
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Need for PBPK Modeling for Therapeutic Proteins --
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PBPK Modeling for Therapeutic Proteins --
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Pharmacokinetic Scaling --
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Applications of PBPK Models of Therapeutic Proteins --
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PBPK Integration with Pharmacodynamics --
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Antisense Oligonucletides and RNA Interferance --
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Antisense Oligonucletides (ASOs) --
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Ribonucleic Acid Interference (RNAi) --
,
Pharmacokinetics of ASOs50 and Double-Stranded RNAs --
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Design and Modifications of ASOs to Improve Target Affinity and PD: the First, Second, and Third Generation ASOs --
,
Integration of PK/PBPK and PD Modeling --
,
Keywords --
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References --
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APPLICATIONS IN THE PHARMACEUTICAL INDUSTRY --
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Data Integration And Sensitivity Analysis --
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Introduction --
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Examples of Data Integration with PBPK Modeling --
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Examples of Sensitivity Analysis with PBPK Modeling --
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References --
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Hypothesis Generation And Pharmacokinetic Predictions --
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Introduction --
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PBPK Simulations of Pharmacokinetic Profiles for Hypothesis Generation and Testing --
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Methodology --
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In Vivo Solubility --
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Delayed Gastric Emptying --
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Regional Variation in Intestinal Loss: Gut Wall Metabolism, Intestinal Efflux, and Luminal Degradation --
,
Enterohepatic Recirculation --
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Inhibition of Drug-Metabolizing Enzymes --
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Inhibition of Hepatic Uptake --
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Inhibition of Hepatobiliary Efflux --
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Pharmacokinetic Predictions --
,
Human Predictions from Preclinical Data --
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Pharmacokinetic Predictions in Clinical Development --
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References --
,
Integration Of Pbpk And Pharmacodynamics --
,
Introduction --
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Pharmacodynamic Principles --
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Pharmacological Targets and Drug Action --
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Functional Adaptation Processes: Tolerance, Sensitization, and Rebound (Fig 13.2) --
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Pharmacodynamic Modeling --
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Concentration -- Effect, Dose -- Response Curves, and Sigmoid Emax Models --
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Mechanism-Based PD Modeling --
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Simple Direct Effects --
,
Models Accommodating Delayed Pharmacological Response --
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Models Accommodating Nonlinearity in Pharmacological Response with Respect to Time --
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Pharmacokinetic Modeling: Compartmental PK and PBPK --
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Integration of PK or PBPK with PD Modeling --
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Reasons for Poor PK/PD Correlation --
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Applications of PK or PBPK/PD Modeling in Drug Discovery and Development --
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Need for a Mechanistic PBPK/PD Integration --
,
Applications of PK or PBPK/PD in Drug Discovery --
,
Applications of PK or PBPK/PD in Drug Development --
,
Regulatory Perspective --
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Conclusions --
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Keywords --
,
References --
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Physiologically-Based Pharmacokinetic Modeling Of Populations --
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Introduction --
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Population Modeling with PBPK --
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Healthy to Target Patient Population: Impact of Disease on Pharmacokinetics --
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Modeling Subpopulations: Impact of Age, Gender, Co-morbidities, and Genetics on Pharmacokinetics --
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Personalized Medicine with PBPK/PD --
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Keyword --
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References --
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PBPK Models Along The Drug Discovery And Development Value Chain
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Summary of Applications of PBPK Models along Value Chain --
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Obstacles and Future Directions for PBPK Modeling --
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Keyword --
,
References.
Additional Edition:
Print version: Peters, Sheila Annie. Physiologically-based pharmacokinetic (PBPK) modeling and simulations Hoboken, N.J. : Wiley, c2012 ISBN 9780470484067
Language:
English
Keywords:
Electronic books.
;
Electronic books.
URL:
https://onlinelibrary.wiley.com/doi/book/10.1002/9781119497813
URL:
https://onlinelibrary.wiley.com/doi/book/10.1002/9781119497813
URL:
https://onlinelibrary.wiley.com/doi/book/10.1002/9781119497813