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Physiologically-Based Pharmacokinetic (PBPK) Modeling and Simulations

Physiologically-Based Pharmacokinetic (PBPK) Modeling and Simulations
Principles, Methods, and Applications in the Pharmaceutical Industry

by Sheila Annie Peters

  • Publisher : John Wiley & Sons
  • Release : 2012-02-17
  • Pages : 450
  • ISBN : 1118140303
  • Language : En, Es, Fr & De
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The only book dedicated to physiologically-based pharmacokineticmodeling in pharmaceutical science Physiologically-based pharmacokinetic (PBPK) modeling has becomeincreasingly widespread within the pharmaceutical industry over thelast decade, but without one dedicated book that provides theinformation researchers need to learn these new techniques, itsapplications are severely limited. Describing the principles,methods, and applications of PBPK modeling as used inpharmaceutics, Physiologically-Based Pharmacokinetic (PBPK)Modeling and Simulations fills this void. Connecting theory with practice, the book explores theincredible potential of PBPK modeling for improving drug discoveryand development. Comprised of two parts, the book first provides adetailed and systematic treatment of the principles behindphysiological modeling of pharmacokinetic processes,inter-individual variability, and drug interactions for smallmolecule drugs and biologics. The second part looks in greaterdetail at the powerful applications of PBPK to drug research. Designed for a wide audience encompassing readers looking for abrief overview of the field as well as those who need more detail,the book includes a range of important learning aids. Featuringend-of-chapter keywords for easy reference—a valuable assetfor general or novice readers without a PBPK background—alongwith an extensive bibliography for those looking for furtherinformation, Physiologically- Based Pharmacokinetic (PBPK) Modelingand Simulations is the essential single-volume text on one of thehottest topics in the pharmaceutical sciences today.

Translational Physiologically-based Pharmacokinetic (PBPK) Modeling and Simulation to Support Drug Development and Pharmacotherapy

Translational Physiologically-based Pharmacokinetic (PBPK) Modeling and Simulation to Support Drug Development and Pharmacotherapy
A Book

by Anonim

  • Publisher : Unknown Publisher
  • Release : 2018
  • Pages : 129
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Physiologically Based Pharmacokinetic (PBPK) Model Development of Perfluorocarboxylic Acids for Rats and Humans

Physiologically Based Pharmacokinetic (PBPK) Model Development of Perfluorocarboxylic Acids for Rats and Humans
A Book

by 晴美

  • Publisher : Unknown Publisher
  • Release : 2013
  • Pages : 129
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Physiologically Based Pharmacokinetic Modeling

Physiologically Based Pharmacokinetic Modeling
Science and Applications

by Micaela Reddy,R. S. Yang,Melvin E. Andersen,Harvey J. Clewell III

  • Publisher : John Wiley & Sons
  • Release : 2005-06-14
  • Pages : 420
  • ISBN : 0471478776
  • Language : En, Es, Fr & De
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A definitive, single source of information on PBPK modeling Physiologically-based pharmacokinetic (PBPK) modeling is becomingincreasingly important in human health risk assessments and insupporting pharmacodynamic modeling for toxic responses. Organizedby classes of compounds and modeling purposes so users can quicklyaccess information, this is the first comprehensive reference ofits kind. This book presents an overview of the underlying principles of PBPKmodel development. Then it provides a compendium of PBPK modelinginformation, including historical development, specific modelingchallenges, and current practices for: * Halogenated Alkanes * Halogenated Alkenes * Alkene and Aromatic Compounds * Reactive Vapors in the Nasal Cavity * Alkanes, Oxyhydrocarbons, and Related Compounds * Pesticides and Persistent Organic Pollutants * Dioxin and Related Compounds * Metals and Inorganic Compounds * Drugs * Antineoplastic Agents * Perinatal Transfer * Mixtures * Dermal Exposure Models In addition to pinpointing specific information, readers canexplore diverse modeling techniques and applications. Anauthoritative reference for toxicologists, ecotoxicologists, riskassessors, regulators, pharmacologists, pharmacists, and graduatestudents in pharmacokinetics and toxicology, Physiologically-BasedPharmacokinetic Modeling compiles information from leaders in thefield and discusses future directions for PBPK modeling.

Physiologically-Based Pharmacokinetic/Toxicokinetic Modeling in Risk Assessment

Physiologically-Based Pharmacokinetic/Toxicokinetic Modeling in Risk Assessment
A Book

by Anonim

  • Publisher : Unknown Publisher
  • Release : 2005
  • Pages : 40
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Physiologically-based pharmacokinetic (PBPK) modeling has become the tool of choice to develop estimates of target site dosimetries in animals and humans for risk assessment purposes. PBPK model compartments correspond directly to the tissues and organs in the species. The drawbacks of PBPK modeling primarily relate to the time, effort and cost involved in appropriately developing, validating and applying a model. We outline some of the practical issues involved in the appropriate development of a PBPK model. Among the first models to be developed and used for risk assessment were those for volatile organics. These basic models are discussed in this report. For some chemicals, however, simpler models are not enough to adequately describe the data. We discuss some of the issues involved in the development of more complex PBPK models. Issues may include more detailed modeling of metabolic processes and specific organs; changes in physiology due to development, pregnancy or aging (life-stage modeling); and interactions between more than one chemical. It may also be necessary to interface the pharmacokinetic models with models of the interaction of the chemical with the target tissue (pharmacodynamic PD models) in order to provide a more complete description of the overall process. Certain experimental techniques are central to the successful development of PBPK models. These include methods to experimentally determine blood and tissue partition coefficients, metabolic parameters, and exposure kinetics.

Approaches for the Application of Physiologically Based Pharmacokinetic (PBPK) Models and Supporting Data in Risk Assessment

Approaches for the Application of Physiologically Based Pharmacokinetic (PBPK) Models and Supporting Data in Risk Assessment
A Book

by Anonim

  • Publisher : Unknown Publisher
  • Release : 2006
  • Pages : 123
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Physiologically Based Pharmacokinetic Modeling

Physiologically Based Pharmacokinetic Modeling
A Book

by Jasmine Davda

  • Publisher : LAP Lambert Academic Publishing
  • Release : 2009-08
  • Pages : 112
  • ISBN : 9783838309705
  • Language : En, Es, Fr & De
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This book describes the application of physiologically based pharmacokinetic (PBPK) modeling to characterize the disposition of therapeutic monoclonal antibodies (MAbs). These macromolecules exhibit distinctly different pharmacokinetic features compared with conventional small-molecule drugs. A PBPK model was developed to characterize the biodistribution of the pancarcinoma MAb CC49 in normal and neoplastic tissues of nude mice. The model included all the major processes involved in determining the disposition characteristics of MAbs. The applicability of the model was tested by predicting the disposition of di- and tetravalent scFv constructs of CC49 in mice. Further, the model was applied to study the differences in disposition between Mabs labeled with 125I and 177Lu. Finally, the clinical utility of the model was tested by attempting to predict the disposition and tumor uptake of CC49 in patients. This model may be used to study the biodistribution and tumor localization of different combinations of radionuclides and engineered antibody fragments in an effort to establish the most effective approach to achieve the optimal therapeutic ratio for tumor therapy.

CYP450-mediated Drug-drug Interactions

CYP450-mediated Drug-drug Interactions
Towards Prediction and Informed Dose Recommendation Using Physiologically-based Pharmacokinetic (PBPK) Modeling

by Niloufar Marsousi

  • Publisher : Unknown Publisher
  • Release : 2017
  • Pages : 214
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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A Parameter Analysis of a Physiologically Based Pharmacokinetic (PBPK) Model Describing the Movements of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the Mouse

A Parameter Analysis of a Physiologically Based Pharmacokinetic (PBPK) Model Describing the Movements of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the Mouse
A Book

by Jessica Leigh Wagner

  • Publisher : Unknown Publisher
  • Release : 2017
  • Pages : 60
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Uncertainty and Variability in Physiologically-based Pharmacokinetic (PBPK) Models

Uncertainty and Variability in Physiologically-based Pharmacokinetic (PBPK) Models
Key Issues and Case Studies (final Report).

by Anonim

  • Publisher : Unknown Publisher
  • Release : 2008
  • Pages : 9
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Inhibition of the Sodium-iodide Symporter by Perchlorate

Inhibition of the Sodium-iodide Symporter by Perchlorate
An Evaluation of Life Stage Sensitivity Using Physiologically Based Pharmacokinetic (PBPK) Modeling

by Anonim

  • Publisher : Unknown Publisher
  • Release : 2009
  • Pages : 78
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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This report provides an analysis of perchlorate-mediated inhibition of the sodium-iodide symporter (NIS) in humans using published PBPK models, focusing on the degree of NIS inhibition as a function of lifestage. The models provide information that may be used to address differences in human responses to perchlorate across lifestages.

Use of Physiologically Based Pharmacokinetic Models to Quantify the Impact of Human Age and Interindividual Differences in Physiology and Biochemistry Pertinent to Risk

Use of Physiologically Based Pharmacokinetic Models to Quantify the Impact of Human Age and Interindividual Differences in Physiology and Biochemistry Pertinent to Risk
A Book

by John C. Lipscomb,Gregory L. Kedderis,United States. Environmental Protection Agency. Office of Research and Development,National Center for Environmental Assessment (Cincinnati, Ohio)

  • Publisher : Unknown Publisher
  • Release : 2006
  • Pages : 234
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Physiologically-Based Pharmacokinetic (PBPK) Models for the Description of Sequential Metabolism of Codeine to Morphine and Morphine 3-Glucuronide (M3G) in Man and Rat

Physiologically-Based Pharmacokinetic (PBPK) Models for the Description of Sequential Metabolism of Codeine to Morphine and Morphine 3-Glucuronide (M3G) in Man and Rat
A Book

by Shu Chen

  • Publisher : Unknown Publisher
  • Release : 2010
  • Pages : 250
  • ISBN : 9780494725412
  • Language : En, Es, Fr & De
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Whole-body PBPK models were developed based on both the intestinal traditional model (TM) and segregated-flow model (SFM) to describe codeine sequential metabolism in man/rat. Model parameters were optimized with ScientistRTM and SimcypRTM simulator to predict literature data after oral (p.o.) and intravenous (i.v.) codeine administration in man/rat. In vivo codeine PK studies on rats were performed to provide more data for simulation. The role of fm' (fractional formation clearance of morphine from codeine) in model discrimination between the TM and SFM was investigated. A greater difference between the [AUC M3G/AUCMorphine]p.o. and [ AUCM3G/AUCMorphine]i.v. ratio existed for the SFM, especially when the fm' was low. It was found that our tailor-made PBPK models using ScientistRTM were superior to those from SimcypRTM in describing codeine sequential metabolism. Residual sum of squares and AUC's were calculated for each model, which demonstrated superiority of the SFM over TM in predicting codeine sequential metabolism in man/rat.

Providing a Theoretical Basis for Nanotoxicity Risk Analysis Departing from Traditional Physiologically-based Pharmacokinetic (PBPK) Modeling

Providing a Theoretical Basis for Nanotoxicity Risk Analysis Departing from Traditional Physiologically-based Pharmacokinetic (PBPK) Modeling
A Book

by Dirk P. Yamamoto

  • Publisher : Unknown Publisher
  • Release : 2010
  • Pages : 376
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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A Comparison of Physiologically-Based Pharmacokinetic (PBPK) Models of Methyl-Tertiary Butyl Ether (MTBE)

A Comparison of Physiologically-Based Pharmacokinetic (PBPK) Models of Methyl-Tertiary Butyl Ether (MTBE)
A Book

by Nikki Shavon Smith

  • Publisher : Unknown Publisher
  • Release : 2018
  • Pages : 124
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Consequences of a Lack of Adult Intravenous Data on the Prediction Accuracy of Pediatric Physiologically Based Pharmacokinetic (PBPK) Modeling

Consequences of a Lack of Adult Intravenous Data on the Prediction Accuracy of Pediatric Physiologically Based Pharmacokinetic (PBPK) Modeling
A Book

by Rabiya Chandani

  • Publisher : Unknown Publisher
  • Release : 2015
  • Pages : 130
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Lack of pediatric clinical data has led to a large gap in knowledge concerning drug efficacy, safety and dosing guidelines within the pediatric population. Many pediatric off-label doses are based largely on adult studies with little or no pediatric experience; this has the potential to lead to treatment failures, toxicities, and various other drug-related adverse events. Given that recruitment to pediatric trials is difficult, researchers have recently used physiologically-based pharmacokinetic (PBPK) models as a means to efficiently plan pediatric clinical studies. PBPK models are mechanistic in nature and mathematically describe the disposition of drugs in an organism. This in silico technique predicts pharmacokinetic (PK) profiles based on compound physicochemical properties and multiple physiological input parameters of the individual, such as organ volumes, tissue composition, blood flow, and clearance (CL). Pediatric PK parameters are typically predicted using a pediatric PBPK model that has been developed using an adult PBPK model and clinical PK data. Within this workflow for pediatric PBPK model development, adult intravenous (IV) data is typically used; however, there are many instances where there may not be an IV formulation available for certain compounds. As a result, the question remains if the workflow for pediatric PBPK modeling produces accurate pediatric PK predictions in the absence of adult IV data. In this case, IV data from pre-clinical species (i.e. rat) may be an alternative to human IV data. The objective of this study was to assess the ability of pediatric PBPK models to predict observed pediatric PK parameters using a model development workflow that uses rat IV PK data, as opposed to adult human IV PK data. The implications of both workflows were assessed by comparing the precision and bias of the predicted vs. observed PK exposure metrics in children. This study demonstrated that rat IV data is a viable alternative to using adult IV PK data within the pediatric PBPK model development workflow and the majority of exposure metrics were within 2 fold from the observed pediatric data, regardless of workflow or Biopharmaceutics Classification System (BCS) class of the compound. Ultimately, the model was not hindered in its prediction accuracy, despite a lack of distribution and clearance data that would otherwise have been derived from human IV data. Overall, the application of rat IV data as a substitute for human IV data in PBPK modeling is a novel approach that has significant potential for future application.

Physiologically Based Pharmacokinetic (PBPK) Modelling of Cisplatin in Rats and Humans

Physiologically Based Pharmacokinetic (PBPK) Modelling of Cisplatin in Rats and Humans
A Book

by Hyunjin Park

  • Publisher : Unknown Publisher
  • Release : 2019
  • Pages : 129
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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The physiologically based pharmacokinetic (PBPK) modelling has been accepted as one of the most effective mechanistic techniques to analyze pharmacokinetics (PK) of drugs in the drug development process. Its effectiveness in predicting the PK of drugs is important not only to the current drug development industry but also to potential growth of the pharmaceutical industry as it helps resolve ethical challenges. The PK of cisplatin as an anticancer drug, and its metabolic disposition are investigated by proposing a PBPK modelling framework. A plausible PBPK model is developed to test and validate its predictive utility for extrapolation to other species with the drug. Building and testing a PBPK modelling workflow for translating from rat to human PK scenarios for cisplatin is particularly emphasized. Moreover, this workflow may be helpful to studying and understanding the PK of cisplatin analogues in future studies. In this thesis, the PK of cisplatin is quantitatively studied by employing the PBPK modelling technique, and the modality of interspecies extrapolation from rat models to human models is then tested. As the metabolic mechanism of cisplatin is not evidently revealed, several assumptions have been made to successfully construct the PBPK model which would closely reproduce observed PK data of cisplatin for rats as well as for humans. Based on these assumptions, several parameters which define cisplatin ADME in an organism are reasonably selected. These parameters are optimized based on observed rat PK data by using a numerical optimization process. The PBPK model constructed based on the rat PK data is then evaluated by means of validating the optimized values of the parameters through comparing the PK simulations with other observed PK data for rats. Lastly, the validity of the model for the predictive performance on humans is assessed by translating the model into a human model and evaluating it based on observed PK data for humans.

Physiologically Based Pharmacokinetic Modeling of Nanoparticles in Rodents

Physiologically Based Pharmacokinetic Modeling of Nanoparticles in Rodents
A Book

by Xiaowan Li

  • Publisher : Unknown Publisher
  • Release : 2017
  • Pages : 26
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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A variety of nanoparticles are under development for medicine, energy, food and cosmetics. Both organic and inorganic nanoparticles are playing an increased role in industrial and medical applications. However, little is known about their distribution and effects on the human body, and as a result concerns exist about potential health risks and safety problems. The long-term aim of this research is to quantify the distribution characteristics of nanoparticles and explore how the physicochemical properties of nanoparticles influence their distribution. A physiologically based pharmacokinetic (PBPK) model was successfully developed to describe the pharmacokinetics and biodistribution of nanoparticles in various tissues and blood of the body. A PBPK model based on permeability-limited distribution from the vasculature to tissue spaces was compared with the PBPK model based on flow-limited distribution using literature values for distribution of nanoparticles. In general, the blood-flow limited model is not accurate enough to explain the complete biodistribution of nanoparticles, whereas the permeability-flow limited model provides a more faithful simulation. We also applied a novel formulation of the PBPK model, in which blood plasma kinetics are decoupled from tissue kinetics, and compared the description to those of traditional, coupled PBPK models. Our model parameterization suggested that the decoupled model method without elimination based on permeability-flow limited model accurately predicted the trends of nanoparticles concentration in both tissue and blood. This could indicate that partition coefficients of tissues combining with blood flow to tissue might have a great influence on the biodistribution of nanoparticles. This work provides a foundation for more accurate PBPK correlation of nanoparticle biodistribution that should be of utility both in the emerging area of nanotoxicology and in the preclinical drug development of nanomedicines.

Investigation of PET-based Treatment Planning in Peptide-receptor Radionuclide Therapy (PRRT) Using a Physiologically Based Pharmacokinetic (PBPK) Model

Investigation of PET-based Treatment Planning in Peptide-receptor Radionuclide Therapy (PRRT) Using a Physiologically Based Pharmacokinetic (PBPK) Model
A Book

by Deni Hardiansyah

  • Publisher : Unknown Publisher
  • Release : 2016
  • Pages : 129
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Development and Evaluation of a Physiologically Based Pharmacokinetic (PBPK) Population Model for Elderly Individuals

Development and Evaluation of a Physiologically Based Pharmacokinetic (PBPK) Population Model for Elderly Individuals
A Book

by Jan-Frederik Schlender

  • Publisher : Unknown Publisher
  • Release : 2019
  • Pages : 129
  • ISBN : 9783843940559
  • Language : En, Es, Fr & De
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