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Dissertations / Theses on the topic 'Physiologically- based pharmacokinetic modeling'

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Published: 4 June 2021

Last updated: 8 February 2022

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1

Fàbrega, Bonadona Francesc. "Physiologically-Based Pharmacokinetic (Pbpk) Modeling of Pcdd/Fs and Pfass in Humans." Doctoral thesis, Universitat Rovira i Virgili, 2014. http://hdl.handle.net/10803/284035.

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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 (PCDD/Fs) i els compostos perfluorats (PFASs). L’objectiu de la present tesis es el desenvolupament de un model PBPK per calcular la concentració de PCDD/Fs

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2

Jonsson, Fredrik. "Physiologically based pharmacokinetic modeling in risk assessment - Development of Bayesian population methods." Doctoral thesis, Solna : National Institute for Working Life (Arbetslivsinstitutet), 2001. http://publications.uu.se/theses/91-7045-599-6/.

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3

Li, Xia [Verfasser]. "Application of population, physiologically based, and semi-physiological pharmacokinetic modeling to assess sources of pharmacokinetic variability in individual drugs / Xia Li." Bonn : Universitäts- und Landesbibliothek Bonn, 2020. http://d-nb.info/121830118X/34.

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4

Nguyen, Quynh Hoa. "Risk assessment for drug degradation products using physiologically-based pharmacokinetic models." Diss., University of Iowa, 2014. https://ir.uiowa.edu/etd/1993.

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Degradation product toxicity is a critical quality issue for a small group of useful drug products--e.g. lidocaine, isoniazid, chlorhexidine, gabapentin. In the traditional risk assessment approaches, a no-observed-adverse-effect level (NOAEL) derived from animal data is determined with the use of generic (and arbitrary) uncertainty factors to obtain an acceptable daily intake. The effects of compound-specific biological complexities and pharmacokinetics are typically not part of the risk calculatio

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5

Ball, Kathryn. "Physiologically based pharmacokinetic modelling of the central nervous system : strategies for drug development." Thesis, Paris 5, 2014. http://www.theses.fr/2014PA05P630.

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Une étape critique au cours du développement de médicaments est la mesure ou la prédiction des concentrations du médicament dans un tissu cible, qui peuvent ensuite être liées à des mesures de leur efficacité ou leur toxicité. Les concentrations de médicaments ne pouvant être mesurées dans le cerveau humain, ils doivent être simulés ou prédits en utilisant des approches alternatives de modélisation. L'objectif de cette thèse est de développer in silico des approches de prédiction combinant à la fois des données précliniques in vitro et in vivo dans un modèle physiologique structuré, avec une s

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6

Tsamandouras, Nikolaos. "Development and applications of physiologically-based pharmacokinetic models for population data analyses." Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/development-and-applications-of-physiologicallybased-pharmacokinetic-models-for-population-data-analyses(5793d86f-75e4-4ed9-89ec-b93e9bc6b2e6).html.

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Physiologically-based pharmacokinetic (PBPK) modelling is traditionally employed to predict drug concentration-time profiles in plasma and tissues using information from physiology/biology, in vitro experiments and in silico predictions. Model-based analysis of population pharmacokinetic (PK) data is rarely performed in such a mechanistic framework, as empirical compartmental models are mainly utilised for this purpose. However, the combination of traditional PBPK methodologies with parameter estimation techniques and non-linear mixed effects modelling is an approach with progressively increas

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7

Wendling, Thierry. "Hierarchical mechanistic modelling of clinical pharmacokinetic data." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/hierarchical-mechanistic-modelling-of-clinical-pharmacokinetic-data(573652c9-d3fb-4233-bea7-7abd7ef48d4b).html.

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Pharmacokinetic and pharmacodynamic models can be applied to clinical study data using various modelling approaches depending on the aim of the analysis. In population pharmacokinetics for instance, simple compartmental models can be employed to describe concentration-time data, identify prognostic factors and interpolate within well-defined experimental conditions. The first objective of this thesis was to illustrate such a ‘semi-mechanistic’ pharmacokinetic modelling approach using mavoglurant as an example of a compound under clinical development. In particular, methods to accurately charac

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Thörn, Helena Anna. "First-pass Intestinal Metabolism of Drugs : Experiences from in vitro, in vivo and simulation studies." Doctoral thesis, Uppsala universitet, Institutionen för farmaci, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-165514.

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The bioavailability of a drug can be described as the fraction of an orally administered dose that reaches the systemic circulation and is often limited by first-pass metabolism in the gut and the liver. It is important to have knowledge about these processes since the systemic blood drug concentration is tightly connected to the effect of the drug. The general aim of this project was to quantitatively examine the role of the intestine in relation to the liver in first-pass metabolism of orally administered drugs. The first-pass metabolism of verapamil and raloxifene was investigated in detail

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9

Dennison, James E. "Physiologically-based pharmacokinetic modeling of simple and complex mixtures of gasoline and the gasoline components n-hexane, benzene, toluene, ethylbenzene, and xylene." Access citation, abstract and download form; downloadable file 10.35 Mb, 2004. http://wwwlib.umi.com/dissertations/fullcit/3131667.

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10

Moj, Daniel Andreas [Verfasser], and Thorsten [Akademischer Betreuer] Lehr. "Translational physiologically-based pharmacokinetic (PBPK) modeling and simulation to support drug development and pharmacotherapy / Daniel Andreas Moj ; Betreuer: Thorsten Lehr." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2018. http://d-nb.info/1159900477/34.

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Moj, Daniel [Verfasser], and Thorsten [Akademischer Betreuer] Lehr. "Translational physiologically-based pharmacokinetic (PBPK) modeling and simulation to support drug development and pharmacotherapy / Daniel Andreas Moj ; Betreuer: Thorsten Lehr." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2018. http://d-nb.info/1159900477/34.

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12

Darwich, Adam Saed. "Physiologically-based pharmacokinetic modelling and simulation of oral drug bioavailability : focus on bariatric surgery patients and mechanism-based inhibition of gut wall metabolism." Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/physiologicallybased-pharmacokinetic-modelling-and-simulation-of-oral-drug-bioavailability-focus-on-bariatric-surgery-patients-and-mechanismbased-inhibition-of-gut-wall-metabolism(182c1e87-670c-4430-82ba-b335f6c13887).html.

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Understanding the processes that govern pre-systemic drug absorption and elimination is of high importance in pharmaceutical research and development, and clinical pharmacotherapy, as the oral route remains the most frequently used route of drug administration. The emergence of systems pharmacology has enabled the utilisation of in silico physiologically-based pharmacokinetic (PBPK) modelling and simulation (M&S) coupled to in vitro-in vivo extrapolation in order to perform extrapolation and exploratory M&S in special populations and scenarios were concerns regarding alterations in oral drug e

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13

Long, Chiau Ming. "Biopharmaceutical considerations and in vitro-in vivo correlations (IVIVCs) for orally administered amorphous formulations." Thesis, University of Bath, 2014. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.629670.

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Dissolution testing and physiological based pharmacokinetic modeling are the essential methods during drug development. However, there is a lack of a sound approach and understanding of the parameter that controls dissolution and absorption of amorphous formulations. Robust dissolution conditions and setup and PBPK models that have a predictability of in vivo results will expedite and facilitate the drug development process. In this project, cefuroxime axetil, CA (Zinnat® as the amorphous formulations); itraconazole, ITR (Sporanox® as the amorphous formulation) and a compound undergoing clinic

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14

Olivares, Morales Andres. "Prediction of oral drug bioavailability : from animal-based extrapolation towards the application of physiologically-based pharmacokinetic modelling and simulation." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/prediction-of-oral-drug-bioavailability-from-animalbased-extrapolation-towards-the-application-of-physiologicallybased-pharmacokinetic-modelling-and-simulation(9a6e9a95-1727-4f06-829d-a96f763fd8c9).html.

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The majority of drugs available on the market are intended to be administered through the oral route. To achieve the desired therapeutic effect, an orally administered drug must first reach the systemic circulation and then its site of action. The fraction of the administered drug that reaches the systemic circulation is known as oral bioavailability and it is the product of the absorption and first-pass metabolism processes occurring in both the GI tract and the liver. The factors controlling bioavailability are manifold –both drug and physiologically related - and their complex interplay is

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15

Khalil, Feras [Verfasser], Stephanie [Akademischer Betreuer] Läer, and Jörg [Akademischer Betreuer] Breitkreutz. "Physiologically Based Pharmacokinetic Modeling in Pediatric Drug Development and Research: Methodology, Applications, and Limitations / Feras Khalil. Gutachter: Stephanie Läer ; Jörg Breitkreutz." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2014. http://d-nb.info/1060823640/34.

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16

Wojtyniak, Jan-Georg [Verfasser]. "Model Informed Drug Development and Precision Dosing for Drug-Drug-Gene-Interactions : Application of Physiologically-Based Pharmacokinetic Modeling / Jan-Georg Wojtyniak." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2021. http://d-nb.info/1237268737/34.

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17

Awasthi, Rakesh. "Application of modeling-based approaches to study the pharmacokinetics and pharmacodynamics of Delta-9-tetrahydrocannabinol (THC) and its active metabolite." Diss., University of Iowa, 2017. https://ir.uiowa.edu/etd/5410.

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The medical use of marijuana is increasing, yet little is known about the exposure-response relationships resulting in its psychoactive effects. Δ9-tetrahydrocannabinol (THC) and its active metabolite (11-hydroxy-THC; THC-OH) are the principal psychoactive components in marijuana. It is well known that the plasma concentrations of the psychoactive components of marijuana do not directly relate to the observed psychoactive effects. The presence of a counter-clockwise hysteresis in the plasma concentrations-effect plot demonstrates a temporal delay between the plasma concentrations and observed

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18

Salem, Farzaneh. "Applications of physiologically based pharmacokinetic modelling to prediction of the likelihood of metabolic drug interactions in paediatric population and studying disparities in pharmacokinetics between children and adults." Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/applications-of-physiologically-based-pharmacokinetic-modelling-to-prediction-of-the-likelihood-of-metabolic-drug-interactions-in-paediatric-population-and-studying-disparities-in-pharmacokinetics-between-children-and-adults(1fdefe9a-037a-4738-b92a-5904a60960db).html.

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Anticipation of drug-drug interactions (DDIs) in the paediatric population are merely based on data generated in adults. Hence decision on avoiding certain combinations or attempts to adjust and manage the doses under combination-therapy are mainly speculative from the knowledge of what occurs in adults. However, due to developmental changes in elimination pathways from birth to adolescents, the assumption of DDIs being similar in adults and children might not be correct. This thesis firstly identifies and quantitatively compares the reported DDIs in paediatric and adult populations through a

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19

Ferreira, Carolina Martins André Oliveira. "Utilização de modelos farmacocinéticos de base fisiológica em estudos toxicológicos." Master's thesis, [s.n.], 2015. http://hdl.handle.net/10284/5154.

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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas<br>Os efeitos adversos decorrentes das interações de substâncias químicas com os organismos, devido a exposição voluntária ou involuntária, são objeto de grande preocupação por parte das autoridades de saúde e da população em geral. Atualmente, os efeitos tóxicos são ainda, responsáveis por uma percentagem significativa das falhas na fase final no desenvolvimento de fármacos. A toxicocinética é normalmente descrita usando dois tipo

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20

Li, Mengyao. "USING SEMIPHYSIOLOGICALLY-BASED PHARMACOKINETIC (SEMI-PBPK) MODELING TO EXPLORE THE IMPACT OF DIFFERENCES BETWEEN THE INTRAVENOUS (IV) AND ORAL (PO) ROUTE OF ADMINISTRATION ON THE MAGNITUDE AND TIME COURSE OF CYP3A-MEDIATED METABOLIC DRUG-DRUG INTERACTIONS (DDI) USING MIDAZOLAM (MDZ) AS PROTOTYPICAL SUBSTRATE AND FLUCONAZOLE (FLZ) AND ERYTHROMYCIN (ERY) AS PROTOTYPICAL INHIBITORS." VCU Scholars Compass, 2016. http://scholarscompass.vcu.edu/etd/4402.

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The purpose of the project was to investigate the impact of IV and PO routes difference for MDZ, a prototypical CYP3A substrate, and two CYP3A inhibitors (CYP3AI) -FLZ and ERY-, on the magnitude and time course of their inhibitory metabolic DDI. Individual semi-PBPK models for MDZ, FLZ and ERY were developed and validated separately, using pharmacokinetic (PK) parameters from clinical/in-vitro studies and published physiological parameters. Subsequently, DDI sub-models between MDZ and CYP3AIs incorporated non-competitive and mechanism-based inhibition (MBI) for FLZ and ERY, respectively, on he

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21

Leding, Albin. "Optimized design recommendation for first pharmacokinetic in vivo experiments for new tuberculosis drugs using pharmacometrics modelling and simulation." Thesis, Uppsala universitet, Institutionen för farmaci, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-447311.

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Tuberculosis, the leading cause of death by a single infection disease caused by bacteria, requires long treatments and the bacteria are prone to develop drug resistance. Therefore, new efficient treatment regiments needs developing, which requires new tools for drug development. A major reason for discontinuance of a drug under development is undesired pharmacokinetic properties. Therefore, it is important to have early information of this, preferably the first time the drug is tested in animals. The first in vivo pharmacokinetic experiment is often done in mice and the only information prese

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22

Forbes, Whitney. "Physiologically-Based Pharmacokinetic Model for Ertapenem." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etd/2342.

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Ertapenem is a carbapenem used to treat a wide range of bacterial infections. What sets ertapenem apart from other carbapenems is its longer half-life which implies it need only be administered once daily. We developed a physiologically-based pharmacokinetic model for the distribution of ertapenem within the body. In the model, parameters such as human body weight and height, age, organ volumes, blood flow rates, and partition coefficients of particular tissues are used to examine the absorption, distribution, metabolism, and excretion of ertapenem. The total and free blood concentrations foun

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23

White, Rebekah. "A Physiologically-Based Pharmacokinetic Model for Vancomycin." Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/honors/308.

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Vancomycin is an antibiotic used for the treatment of systemic infections. It is given intravenously usually every twelve or twenty-four hours. This particular drug has a medium level of boundedness, with approximately fty percent of the drug being free and thus physiologically eective. A physiologically-based pharmacokinetic (PBPK) model was used to better understand the absorption, distribution, and elimination of the drug. Using optimal parameters, the model could be used in the future to test how various factors, such as BMI or excretion levels, might aect the concentration of the antibiot

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Deveau, Michelle Leigh. "Exploration of Contextual Influences on the Incorporation of Chemical- and Scenario-Specific Data in the Derivation of Environmental Health and Occupational Exposure Limits for Chemicals." Thesis, Université d'Ottawa / University of Ottawa, 2021. http://hdl.handle.net/10393/42494.

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Outputs of dose–response assessments can be used as benchmarks that help to identify the need for risk management measures to reduce population health risks associated with exposure to chemicals. Various approaches can be used to facilitate the incorporation of chemical- or scenario-specific data into dose–response analyses, as a means of replacing or influencing default assumptions and extrapolations. The goal of the first part of this thesis was to examine the evolution of approaches to the incorporation of chemical- and scenario-specific data in dose–response assessments in regulatory setti

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25

Alsmadi, Mo'tasem Mohamed. "Physiologically based pharmacokinetic (PBPK) model of Ivermectin (IVM)." Diss., University of Iowa, 2014. https://ir.uiowa.edu/etd/5906.

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Purpose: Ivermectin (IVM) is a lipophilic BCS-II compound (molecular weight=875 g/mole, LogP=3.22, intrinsic solubility=700 ug/L). IVM is used as antiparasitic drug in both humans and animals. IVM is known to have a half-life of 12-56 hours in humans. Strongyloidiasis is a chronic parasitic infection of humans caused by Strongyloides stercoralis, with an estimated 30-100 million people infected worldwide. Infection may be severe and even life-threatening in cases of immunodeficiency. Patients with disseminated strongyloidiasis are usually bedridden hospitalized patients that show symptoms such

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26

Rodrigues, Clare Louise. "Physiologically-based Pharmacokinetic Modelling:Pre-clinical and Clinical Pharnmacokinetic Studies." Thesis, University of Manchester, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.492740.

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Physiologically-based pharmacokinetic (PBPK) modelling is a computational technique which includes the anatomy and physiology of the study species (species-specific information), as well as the physicochemical properties of the study compound (compound-specific informafion). This data-rich situation confers many advantages on drug development and discovery, especially in the areas of extrapolation between species, route IS of administration and doses. However, it remains under-used in drug research. This thesis examines the applications of PBPK modelling in three different scenarios, in the li

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McCartt, Paezha M. "A Physiologically-Based Pharmacokinetic Model for the Antibiotic Levofloxacin." Digital Commons @ East Tennessee State University, 2016. https://dc.etsu.edu/honors/343.

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Levofloxacin is in a class of antibiotics known as fluoroquinolones, which treat infections by killing the bacteria that cause them. A physiologically-based pharmacokinetic (PBPK) model was developed to investigate the uptake, distribution, and elimination of Levofloxacin after a single dose. PBPK modeling uses parameters such as body weight, blood flow rates, partition coefficients, organ volumes, and several other parameters in order to model the distribution of a particular drug throughout the body. Levofloxacin is only moderately bound in human blood plasma, and, thus, for the purposes of

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28

Doddapaneni, Suresh. "A physiologically-based pharmacokinetic and pharmacodynamic model for parathion /." The Ohio State University, 1995. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487861796819578.

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29

Potter, Laura Kay. "Physiologically Based Pharmacokinetic Models for the Systemic Transport of Trichloroethylene." NCSU, 2001. http://www.lib.ncsu.edu/theses/available/etd-20010516-105855.

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<p>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

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Tomaszewska, Irena. "In vitro and physiologically based pharmacokinetic models for pharmaceutical cocrystals." Thesis, University of Bath, 2013. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607145.

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About 30% of commercial and developmental drugs exhibit poor solubility and thus poor bioavailability. Strategies that enhance solubility of such compounds have become more popular. Cocrystallisation is one of these strategies, so characterisation of in vitro performance of cocrystals is essential. Conventional dissolution systems (USP apparatus 1 and USP apparatus 2) are often not suitable for testing poorly soluble drugs due to failure in providing sink conditions and inability to change the media during the experiment. This project involves designing appropriate dissolution methods that wil

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31

Sjögren, Erik. "Hepatic Disposition of Drugs and the Utility of Mechanistic Modelling and Simulation." Doctoral thesis, Uppsala universitet, Institutionen för farmaci, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-132571.

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The elimination of drugs from the body is in many cases performed by the liver. Much could be gained if an accurate prediction of this process could be made early in the development of new drugs. However, for the elimination to occur, the drug molecule needs first to get inside the liver cell. Disposition is the expression used to encapsulate both elimination and distribution. This thesis presents novel approaches and models based on simple in vitro systems for the investigation of processes involved in the hepatic drug disposition. An approach to the estimation of enzyme kinetics based on su

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Turner, Anita L. "A physiologically based pharmacokinetic model for lactational transfer of Na¹³¹I." Diss., Georgia Institute of Technology, 1999. http://hdl.handle.net/1853/17069.

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33

Abbas, Richat R. "A physiologically based pharmacokinetic and pharmacodynamic model for paraoxon in rainbow trout /." The Ohio State University, 1994. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487858417983294.

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34

Dong, Jin. "First-principle based pharmacokinetic modeling." Scholarly Commons, 2016. https://scholarlycommons.pacific.edu/uop_etds/128.

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Predicting drug concentrations in the blood and at the site of action is the hottest topic in pharmacokinetics (PK). In vitro-in vivo extrapolation (IVIVE) and physiological based pharmacokinetics (PBPK) models are two major PK prediction strategies. However, both IVIVE and PBPK models are considered as immature methodologies due to their poor predictability. The goal of the research is to investigate the discrepancies within IVIVE and PBPK predictions according to first-principles: convection, diffusion, metabolism, and carrier-mediated transport. In Chapter 2, non-permeability limited hepati

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Peigné, Sophie. "Evaluation et comparaison de méthodologies pharmacocinétiques en pédiatrie." Thesis, Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCB146.

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Un nouveau règlement (CE) n° 1901/2006 établi par le Parlement européen et le Conseil de l’UE, relatif aux médicaments à usage pédiatrique, vise à améliorer la santé et la qualité de vie des enfants en Europe, en garantissant que les nouveaux médicaments pédiatriques et les médicaments déjà commercialisés seront pleinement adaptés à leurs besoins spécifiques. Ce règlement prévoit de nouvelles obligations pour l'industrie pharmaceutique, assorties de récompenses et d'incitations. Dans ce contexte, un plan d’investigation pédiatrique a été proposé pour l’ivabradine dans plusieurs sous-groupes de

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Fulcher, Benjamin David. "Quantitative Physiologically-Based Sleep Modeling: Dynamical Analysis and Clinical Applications." Science. School of Physics, 2009. http://hdl.handle.net/2123/4347.

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Master of Science<br>In this thesis, a recently developed physiologically-based model of the sleep-wake switch is analyzed and applied to a variety of clinically-relevant protocols. In contrast to phenomenological models, which have dominated sleep modeling in the past, the present work demonstrates the advantages of the physiologically-based approach. Dynamical and linear stability analyses of the Phillips-Robinson sleep model allow us to create a general framework for determining its response to arbitrary external stimuli. The effects of near-stable wake and sleep ghosts on the model’s dynam

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Schlender, Jan-Frederik [Verfasser]. "Development and Evaluation of a Physiologically Based Pharmacokinetic (PBPK) Population Model for Elderly Individuals / Jan-Frederik Schlender." München : Verlag Dr. Hut, 2019. http://d-nb.info/1188515942/34.

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Ling, Melissa Chan Pui. "DEVELOPMENT OF A PHYSIOLOGICALLY BASED PHARMACOKINETIC (PBPK) MODEL FOR ENDOSULFAN AND ITS APPLICATION IN HEALTH RISK ASSESSMENTS." 京都大学 (Kyoto University), 2005. http://hdl.handle.net/2433/138508.

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Kyoto University (京都大学)<br>0048<br>新制・課程博士<br>博士(工学)<br>甲第11874号<br>工博第2567号<br>新制||工||1359(附属図書館)<br>23654<br>UT51-2005-N708<br>京都大学大学院工学研究科環境地球工学専攻<br>(主査)教授森澤眞輔, 教授内山巖雄, 教授伊藤禎彦<br>学位規則第4条第1項該当

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Sall, Carolina. "In vitro-in vivo assessment of repaglinide metabolism and drug-drug interactions : towards a physiologically-based pharmacokinetic model." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/in-vitroin-vivo-assessment-of-repaglinide-metabolism-and-drugdrug-interactionstowards-a-physiologicallybased-pharmacokinetic-model(1b8eca49-bc68-484e-b921-2e324b4c5f00).html.

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Repaglinide is currently recommended as an in vivo CYP2C8 probe by the U.S. Food and Drug Administration (FDA), but the kinetic characterisation and enzymes involved in the elimination of this drug have not been fully delineated. In addition to its complex metabolism, polymorphism in the SLCO1B1 gene encoding for the hepatic uptake transporter organic anion transporting polypeptide 1B1 (OATP1B1) has been shown to impact repaglinide pharmacokinetics, further complicating the prediction of repaglinide clearance and drug-drug interactions (DDIs). The aim of this thesis was to firstly perform a sy

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Saylor, Kyle Lucas. "Computational Evaluation and Structure-based Design for Potentiation of Nicotine Vaccines." Diss., Virginia Tech, 2020. http://hdl.handle.net/10919/100314.

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Existing therapeutic options for the alleviation of nicotine addiction have been largely ineffective at stemming the tide of tobacco use. Immunopharmacotherapy, or vaccination, is a promising, alternate therapy that is currently being explored. Results from previous studies indicate that nicotine vaccines (NVs) are effective in subjects that achieve high drug-specific antibody titers, though overall efficacy has not been observed. Consequently, improvement of these vaccines is necessary before they can achieve approval for human use. In this report, three separate approaches towards NV potenti

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Thompson, Zachary John. "Statistical Estimation of Physiologically-based Pharmacokinetic Models: Identifiability, Variation, and Uncertainty with an Illustration of Chronic Exposure to Dioxin and Dioxin-like-compounds." Scholar Commons, 2012. http://scholarcommons.usf.edu/etd/4241.

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Assessment of human exposure to environmental chemicals is inherently subject to uncertainty and variability. There are data gaps concerning the inventory, source, duration, and intensity of exposure as well as knowledge gaps regarding pharmacokinetics in general. These gaps result in uncertainties in exposure assessment. The uncertainties compound further with variabilities due to population variations regarding stage of life, life style, and susceptibility, etc. Use of physiologically-based pharmacokinetic (PBPK) models promises to reduce the uncertainties and enhance extrapolation between s

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Clark, Kelli J. "Temperature and species comparisons of Benzocaine pharmacokinetics, metabolism and physiologically based pharmacokinetic model within Channel Catfish, Ictalurus Punctatus, and Yellow Perch, Perca Flavescens." The Ohio State University, 1999. http://rave.ohiolink.edu/etdc/view?acc_num=osu1282754462.

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Luu, Kenneth T. "Exploring the time course of brain 5-hydroxytryptamine via mechanism-based pharmacokinetic-pharmacodynamic modeling." Scholarly Commons, 2006. https://scholarlycommons.pacific.edu/uop_etds/2622.

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Serotonin (5-hydroxytryptamine, 5-HT) has been heavily implicated in the pathophysiology of depression and although its changes in the brain has been well studied using microdialysis, the analysis of its time data is often insufficient as pharmacokinetic (PK) and pharmacodynamic (PD) concepts are often neglected. The works in this dissertation attempt to further explore 5-HT time data via mechanism-based PK/PD modeling. The first work explored the dorsal raphe nucleus (DRN) in which the desensitization of 5-HTIA autoreceptors has been implicated in the several-week delay in onset of therapeuti

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Verner, Marc-André, Anne E. Loccisano, Nils-Halvdan Morken, et al. "Associations of Perfluoroalkyl Substances (PFASs) with Lower Birth Weight: An Evaluation of Potential Confounding by Glomerular Filtration Rate Using a Physiologically Based Pharmacokinetic Model (PBPK)." Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/etsu-works/28.

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Background: Prenatal exposure to perfluoroalkyl substances (PFAS) has been associated with lower birth weight in epidemiologic studies. This association could be attributable to glomerular filtration rate (GFR), which is related to PFAS concentration and birth weight. Objectives: We used a physiologically based pharmacokinetic (PBPK) model of pregnancy to assess how much of the PFAS–birth weight association observed in epidemiologic studies might be attributable to GFR. Methods: We modified a PBPK model to reflect the association of GFR with birth weight (estimated from three studies of GFR an

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Bachelet, Delphine. "Biomarqueurs d'exposition aux composés organochlorés et risque de cancer du sein : analyse de l'étude cas-témoins en population générale CECILE basée sur l'utilisation de modèles pharmacocinétiques." Phd thesis, Université Paris Sud - Paris XI, 2012. http://tel.archives-ouvertes.fr/tel-00807245.

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Le cancer du sein est le plus fréquent des cancers de la femme. Son incidence n'est expliquée que partiellement par les facteurs de risque bien établis comme les facteurs reproductifs, hormonaux ou génétiques. Plusieurs éléments suggèrent l'existence de facteurs de risque environnementaux, tels que les polluants organochlorés persistants connus comme perturbateurs endocriniens. Les objectifs de ce travail sont : d'étudier les niveaux d'exposition, et leurs déterminants, au DDE (principal métabolite de l'insecticide DDT) et aux polychlorobiphényles (PCB) ; d'estimer par une modélisation pharmac

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Ruark, Christopher Daniel. "Quantitative Structure-Activity Relationships for Organophosphates Binding to Trypsin and Chymotrypsin." Wright State University / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=wright1278010674.

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Silva, Sílvia Raquel Filipe da. "Farmacocinética do diazepam." Master's thesis, [s.n.], 2013. http://hdl.handle.net/10284/3978.

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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas<br>O diazepam é um princípio ativo do grupo farmacológico das benzodiapezinas, do qual é o mais representativo, sendo por muitos considerado a molécula modelo deste grupo. É largamente utilizado no tratamento de ansiedades e outros distúrbios físicos e psicológicos associados às mesmas. De forma a optimizar os resultados da prática clínica, considerando o factor variabilidade interindividual, é essencial recorrer à monitorização ter

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Rasool, Muhammad Fawad [Verfasser], Stephanie [Gutachter] Läer, and Jörg [Gutachter] Breitkreutz. "Development and Evaluation of Physiologically Based Pharmacokinetic Drug-Disease Models for Carvedilol in Adults and Children by Using Population Based Simulations and Real Data / Muhammad Fawad Rasool. Gutachter: Stephanie Läer ; Jörg Breitkreutz." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2016. http://d-nb.info/1103656708/34.

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Kristoffersson, Anders. "Study Design and Dose Regimen Evaluation of Antibiotics based on Pharmacokinetic and Pharmacodynamic Modelling." Doctoral thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-264798.

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Current excessive use and abuse of antibiotics has resulted in increasing bacterial resistance to common treatment options which is threatening to deprive us of a pillar of modern medicine. In this work methods to optimize the use of existing antibiotics and to help development of new antibiotics were developed and applied. Semi-mechanistic pharmacokinetic-pharmacodynamic (PKPD) models were developed to describe the time course of the dynamic effect and interaction of combinations of antibiotics. The models were applied to illustrate that colistin combined with a high dose of meropenem may ove

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Seabra, Carolina Isabel Ribeiro. "Farmacocinética do ibuprofeno." Master's thesis, [s.n.], 2015. http://hdl.handle.net/10284/5305.

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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas<br>O ibuprofeno é um anti-inflamatório não esteroide (AINE) da família dos derivados arilpropiónicos usado no tratamento sintomático de artrite reumatoide, osteoartrite, tendinite e bursite aguda principalmente em pacientes com intolerância gastrointestinal a outros AINE. A intensidade dos processos de absorção, distribuição, metabolização e excreção varia com o tempo; por esta razão, a quantidade de fármaco no organismo, també

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