Skip to main content

Physiologically Based Pharmacokinetic Pbpk Modeling

In Order to Read Online or Download Physiologically Based Pharmacokinetic Pbpk Modeling Full eBooks in PDF, EPUB, Tuebl and Mobi you need to create a Free account. Get any books you like and read everywhere you want. Fast Download Speed ~ Commercial & Ad Free. We cannot guarantee that every book is in the library!

Physiologically Based Pharmacokinetic Modeling

Physiologically Based Pharmacokinetic Modeling Book
Author : Micaela Reddy,R. S. Yang,Melvin E. Andersen,Harvey J. Clewell III
Publisher : John Wiley & Sons
Release : 2005-06-14
ISBN : 0471478776
Language : En, Es, Fr & De

GET BOOK

Book Description :

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 PBPK Modeling and Simulations

Physiologically Based Pharmacokinetic  PBPK  Modeling and Simulations Book
Author : Sheila Annie Peters
Publisher : John Wiley & Sons
Release : 2012-02-17
ISBN : 1118140303
Language : En, Es, Fr & De

GET BOOK

Book Description :

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.

Physiologically Based Pharmacokinetic PBPK Modeling

Physiologically Based Pharmacokinetic  PBPK  Modeling Book
Author : Jeffrey W. Fisher,Jeffery M. Gearhart,Zhoumeng Lin
Publisher : Academic Press
Release : 2020-06-04
ISBN : 0128185961
Language : En, Es, Fr & De

GET BOOK

Book Description :

Physiologically Based Pharmacokinetic (PBPK) Modeling: Methods and Applications in Toxicology and Risk Assessment presents foundational principles, advanced techniques and applications of PBPK modeling. Contributions from experts in PBPK modeling cover topics such as pharmacokinetic principles, classical physiological models, the application of physiological models for dose-response and risk assessment, the use of in vitro information, and in silico methods. With end-of-chapter exercises that allow readers to practice and learn the skills associated with PBPK modeling, dose-response, and its applications to safety and risk assessments, this book is a foundational resource that provides practical coverage of PBPK modeling for graduate students, academics, researchers, and more. Provides end-of-chapter exercises to teach hands-on computational tools used in toxicology Supplies computer code and explanations and includes examples of applied models used in regulatory toxicology and research Authored by expert editors and contributors who are among the best PBPK modelers in the world

Physiologically Based Pharmacokinetic Toxicokinetic Modeling in Risk Assessment

Physiologically Based Pharmacokinetic Toxicokinetic Modeling in Risk Assessment Book
Author : Anonim
Publisher : Unknown
Release : 2005
ISBN : 0987650XXX
Language : En, Es, Fr & De

GET BOOK

Book Description :

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.

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 Book
Author : Anonim
Publisher : Unknown
Release : 2018
ISBN : 0987650XXX
Language : En, Es, Fr & De

GET BOOK

Book Description :

Download Translational Physiologically based Pharmacokinetic PBPK Modeling and Simulation to Support Drug Development and Pharmacotherapy book written by , available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Physiologically Based Pharmacokinetic Modeling

Physiologically Based Pharmacokinetic Modeling Book
Author : Jasmine Davda
Publisher : LAP Lambert Academic Publishing
Release : 2009-08
ISBN : 9783838309705
Language : En, Es, Fr & De

GET BOOK

Book Description :

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.

Physiologically Based Pharmacokinetic Modeling of Nanoparticles in Rodents

Physiologically Based Pharmacokinetic Modeling of Nanoparticles in Rodents Book
Author : Xiaowan Li
Publisher : Unknown
Release : 2017
ISBN : 0987650XXX
Language : En, Es, Fr & De

GET BOOK

Book Description :

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.

Computational Toxicology

Computational Toxicology Book
Author : Patricia Ruiz,Xiaoxia Yang,Annie Lumen,Jeff Fisher
Publisher : Elsevier Inc. Chapters
Release : 2013-06-04
ISBN : 0128060433
Language : En, Es, Fr & De

GET BOOK

Book Description :

Human health risk assessment is “the process to estimate the nature and probability of adverse health effects in humans who may be exposed to chemicals in contaminated environmental media, now or in the future.” Currently, most data required for human risk assessment are derived from toxicological studies conducted in laboratory animals. The “Toxicology in the 21st Century” initiative expands the toxicity testing tools to include the development of alternative toxicity testing methods that examine pathways of toxicity (on a large scale) and the employment of dose-response and extrapolation modeling tools. While the latter methodology is in its infancy, several methodologies for dose-response and extrapolation modeling are more mature. Over the last decade, physiologically based pharmacokinetic (PBPK) modeling has gained acceptance as a computational tool for use in public health assessments. In this chapter, we present examples of quantitative structure-activity relationship (QSAR) models, physiologically based pharmacokinetic (PBPK) models, and biologically based dose response (BBDR) models that have been developed for use in public health assessments and advancing knowledge gained through in silico examinations of biological systems.

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 Book
Author : Rabiya Chandani
Publisher : Unknown
Release : 2015
ISBN : 0987650XXX
Language : En, Es, Fr & De

GET BOOK

Book Description :

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.

Mechanistic Physiologically Based Pharmacokinetic PBPK Modeling of Renal and Systemic Disposition of Drugs and Metabolites

Mechanistic Physiologically Based Pharmacokinetic  PBPK  Modeling of Renal and Systemic Disposition of Drugs and Metabolites Book
Author : Weize Huang
Publisher : Unknown
Release : 2020
ISBN : 0987650XXX
Language : En, Es, Fr & De

GET BOOK

Book Description :

Physiologically-based pharmacokinetic (PBPK) models integrate system specific anatomy and physiology information with drug specific physicochemical and pharmacokinetic properties to predict drug disposition. Such integration permits items, events, processes, and pathways to communicate and influence each other interactively. By taking advantage of such mechanistic nature of PBPK modeling, drug dispositions under untested scenarios could be predicted by extrapolation from observed data in known conditions. Renal clearance is one of the major pathways governing drug dispositions, which has three main mechanisms: unbound filtration, passive reabsorption, and active secretion. In comparison to intestinal absorption and hepatic metabolism, renal clearance has been relatively underappreciated. Controlled clinical experiments that test renal clearance changes under altered conditions and mechanisms have been primarily focusing on drug-drug interaction on active secretion. However, huge gaps in understanding renal clearance still exist in other areas such as altered urine pH and impaired renal function. Further, passive reabsorption has not been paid significant attention by the pharmaceutical field. Therefore, the overarching goal of this thesis is to leverage mechanistic PBPK modeling technique to understand and predict renal clearance of drugs and metabolites under altered urine pH and impaired renal function, with a special focus on compounds undergoing significant renal passive reabsorption. In Chapter 2, to predict the spatiodynamic process of renal passive reabsorption in human, we developed a dynamic physiologically-based mechanistic kidney model based on human data that can integrate drug permeability, tubular surface area, ionization status, and drug concentration gradient between lumen and system to estimate renal passive reabsorption and predict renal clearance of drugs. Using 46 test compounds with a variety of physicochemical properties, the model successfully predicted the renal clearances of 87% compounds within 2-fold and 98% compounds within 3-fold. Further, by incorporating active secretion, the model also successfully predicted the renal clearances of para-aminohippuric acid (PAH), cimetidine, salicylic acid, and memantine. In Chapter 3, to ensure the simulation output from PBPK models can be meaningfully compared to the arm vein plasma drug concentrations collected in clinical studies, we developed a forearm model that captures the tissue distribution at the peripheral sampling site using human arm physiology data, allowing for a better prediction of plasma drug concentrations that are comparable to observed data. The model was successfully verified using arterial and venous concentrations of nicotine, ketamine, lidocaine, and fentanyl simultaneously. Further, I demonstrated that use of a discrepant sampling site in PBPK modeling than observed clinical studies may lead to biased model evaluation, erroneous model parameterization, and misleading prediction in unstudied clinical scenarios. In Chapter 4, to predict the altered renal excretion and systemic AUC of drug and metabolite when urine pH is changed, the mechanistic kidney model developed and verified from Chapter 2 was integrated with the peripheral arm sampling and full body PBPK model developed from Chapter 3. The model was successfully verified with methamphetamine and amphetamine under varying urine pH statuses, and showed feasibility to predict quantitatively and clinically significant changes in drug and metabolite disposition under comedications and diseases that can alter urine pH. In Chapter 5, to predict renal clearance in patients with impaired renal function such as chronic kidney diseases, physiological changes in tubular flow and urine flow observed in chronic kidney disease patients were incorporated into the mechanistic kidney model developed and verified from Chapter 2. The model accounts for the adaptive renal tubular filtrate flows that decrease disproportionately with glomerular filtration rate, and was successfully verified using three parent-metabolite pairs, six non-permeable drugs, six permeable drugs, and two secreted drugs. In conclusion, in this thesis, I developed and verified a physiologically-based mechanistic kidney model to translate drug properties such as plasma protein binding, transcellular permeability, and active transport into renal clearance of drugs and metabolites. This mechanistic kidney model allows prediction of alterations in renal clearance of drugs and metabolites upon changes in urine pH and renal functions, and can be incorporated into a full-body PBPK model to predict alterations in systemic disposition of drugs and metabolites.

CYP450 mediated Drug drug Interactions

CYP450 mediated Drug drug Interactions Book
Author : Niloufar Marsousi
Publisher : Unknown
Release : 2017
ISBN : 0987650XXX
Language : En, Es, Fr & De

GET BOOK

Book Description :

Download CYP450 mediated Drug drug Interactions book written by Niloufar Marsousi, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

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 Book
Author : Jessica Leigh Wagner
Publisher : Unknown
Release : 2017
ISBN : 0987650XXX
Language : En, Es, Fr & De

GET BOOK

Book Description :

Download A Parameter Analysis of a Physiologically Based Pharmacokinetic PBPK Model Describing the Movements of 2 3 7 8 tetrachlorodibenzo p dioxin in the Mouse book written by Jessica Leigh Wagner, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

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 Book
Author : Dirk P. Yamamoto
Publisher : Unknown
Release : 2010
ISBN : 0987650XXX
Language : En, Es, Fr & De

GET BOOK

Book Description :

Download Providing a Theoretical Basis for Nanotoxicity Risk Analysis Departing from Traditional Physiologically based Pharmacokinetic PBPK Modeling book written by Dirk P. Yamamoto, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Physiologically Based Pharmacokinetic Models for the Systemic Transport of Trichloroethylene

Physiologically Based Pharmacokinetic Models for the Systemic Transport of Trichloroethylene Book
Author : Anonim
Publisher : Unknown
Release : 2001
ISBN : 0987650XXX
Language : En, Es, Fr & De

GET BOOK

Book Description :

Three physiologically based pharmacokinetic (PBPK) models for thesystemic transport of inhaled trichloroethylene (TCE) are presented. The major focus ofthese modeling efforts is the disposition of TCE in the adiposetissue, where TCE is known to accumulate. Adipose tissue is highly heterogeneous, with wide variations in fat cell size, lipid composition, blood flow rates and cellpermeability. Since TCE is highly lipophilic, the uneven distributionof lipids in the adipose tissue may lead to an uneven distribution of TCEwithin the fat. These physiological characteristics suggest that thedynamics of TCE in the adipose tissue may depend on spatial variations within the tissue itself. The first PBPK model for inhaled TCE presented here is a system ofordinary differential equations which includes the standardperfusion-limited compartmental model for each of the adipose, brain, kidney, liver, muscle and remaining tissue compartments. Model simulations predict relatively rapiddecreases in TCE fat concentrations following exposure, which may notreflect the accumulation and relative persistence of TCE inside the fattissue. The second PBPK model is identical to the first except forthe adipose tissue compartment, which is modeled as a diffusion-limited compartment. Although this model yields various concentration profiles for TCE inthe adipose tissue depending on the value of the permeabilitycoefficient, this model may not be physically appropriate for TCE, which is highly lipophilic and has a low molecular weight. Moreover, neither of these two PBPK models is able to capture spatialvariation of TCE concentrations in adipose tissue as suggested bythe physiology. The third model we present is a hybrid PBPK model with adispersion-type model for the transport of TCE in the adipose tissue. Thedispersion model is designed to account for the heterogeneities within fattissue, as well as the corresponding spatial variation of TCE concentrationsthat may occur. This partial differential equation.

Physiologically Based Pharmacokinetic Modeling of Skin Absorption Using Dermal Subcompartments

Physiologically Based Pharmacokinetic Modeling of Skin Absorption Using Dermal Subcompartments Book
Author : Anonim
Publisher : Unknown
Release : 1995
ISBN : 0987650XXX
Language : En, Es, Fr & De

GET BOOK

Book Description :

Dermal penetration of chemicals and drugs is important to both toxicologists and pharmacologists. Drug developers try to enhance and environmental professionals try to limit penetration of chemicals through the skin. Both can use predictive biologically-based mathematical models to assist in understanding the processes involved. When these models are based on physiological and biochemical parameters which can be measured in the laboratory, they can be extremely useful. Appropriately validated models based on first principles can be predictive of human exposures when the processes involved are adequately understood. In this thesis we develop four new physiologically-based pharmacokinetic (PBPK) models to predict blood concentrations of dibromomethane (DBM) in rats after neat liquid and vapor exposure. These four new models expand previously developed homogeneous models by adding skin subcompartments. These new models improve the prediction of the blood concentrations especially early in the exposure. Sensitivity analysis shows that one of the permeability constants followed by the blood air partition coefficient have the most impact on blood concentration predictions. With proper validation the new models could be used to improve species, dose, and duration extrapolations of chemical or drug penetration. They could also be used to investigate and predict concentrations of drugs or chemicals in different parts of the skin.

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 Book
Author : Shu Chen
Publisher : Unknown
Release : 2010
ISBN : 9780494725412
Language : En, Es, Fr & De

GET BOOK

Book Description :

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.

Physiologically based Pharmacokinetic PBPK Modeling of PC01 FS and PFASS in Humans

Physiologically based Pharmacokinetic  PBPK  Modeling of PC01 FS and PFASS in Humans Book
Author : Francesc Fàbrega Bonadona,Universitat Rovira i Virgili. Departament d'Enginyeria Química,Universitat Rovira i Virgili. Escola Tècnica Superior d'Enginyeria Química
Publisher : Unknown
Release : 2014
ISBN : 0987650XXX
Language : En, Es, Fr & De

GET BOOK

Book Description :

Els models farmacocinètics (PBPK) són representacions matemàtiques del cos humà, que tenen com a objectiu calcular la concentració de compostos químics en els teixits humans. Els models PBPK poden millorar el càlcul del risc per a la salut humana, però de moment no han estat escassament utilitzats. Entre els compostos ambientals més perillosos per a la salut humana destaquen les dibenzo-p-dioxines policlorades i dibenzofurans policlorats (PC01/Fs) i els compostos perfluorats (PFASs). L'objectiu de la present tesis es el desenvolupament de un model PBPK per calcular la concentració de PC01/Fs i PFASs en teixits humans. Prèviament al desenvolupament del model PBPK, es va desenvolupar un índex de risc utilitzant mapes auto-organitzats (SOM), per calcular els compostos ambientals més perillosos per a la salut humana. Entre els compostos més perillosos es van trobar els PFASs. Després es va desenvolupar el model PBPK per predir les concentracions de PC01/Fs en sang i en teixit adipós. Els resultats finals van ser altament coincidents amb els resultats experimentals trobats a l'àrea de Tarragona (NE d'Espanya), y per això es va considerar el model com a validat. A continuació el model es va adaptar per calcular les concentracions de PFASs. Per això, primer es va adaptar el model per PFOS i PFOA, que són els compostos perfluorats més estudiats en la literatura, i després es va estendre el model a 9 PFASs més. Finalment, es va fer un anàlisis de la incertesa del model PBPK, i la incertesa paramètrica es va estudiar visual i estadísticament.

Physiologically Based Pharmacokinetic PBPK Modeling

Physiologically Based Pharmacokinetic  PBPK  Modeling Book
Author : Jeffrey W. Fisher,Jeffery M. Gearhart,Zhoumeng Lin
Publisher : Academic Press
Release : 2020-05-20
ISBN : 0128196823
Language : En, Es, Fr & De

GET BOOK

Book Description :

Physiologically Based Pharmacokinetic (PBPK) Modeling: Methods and Applications in Toxicology and Risk Assessment presents foundational principles, advanced techniques and applications of PBPK modeling. Contributions from experts in PBPK modeling cover topics such as pharmacokinetic principles, classical physiological models, the application of physiological models for dose-response and risk assessment, the use of in vitro information, and in silico methods. With end-of-chapter exercises that allow readers to practice and learn the skills associated with PBPK modeling, dose-response, and its applications to safety and risk assessments, this book is a foundational resource that provides practical coverage of PBPK modeling for graduate students, academics, researchers, and more. Provides end-of-chapter exercises to teach hands-on computational tools used in toxicology Supplies computer code and explanations and includes examples of applied models used in regulatory toxicology and research Authored by expert editors and contributors who are among the best PBPK modelers in the world

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 Book
Author : Jan-Frederik Schlender
Publisher : Unknown
Release : 2019
ISBN : 9783843940559
Language : En, Es, Fr & De

GET BOOK

Book Description :

Download Development and Evaluation of a Physiologically Based Pharmacokinetic PBPK Population Model for Elderly Individuals book written by Jan-Frederik Schlender, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.