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Showing 1 to 20 of 23 for “"PBPK"”.
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Physiologically-Based Pharmacokinetic (PBPK) Modeling for the Preclinical Development of Spectinamide Antibiotics
… used a physiologically-based pharmacokinetic (PBPK) approach for the prediction of drug pharmacokinetics in organs/tissues of interest and extrapolate their disposition across different species. In the current study, we built, qualified, and refined a minimalistic PBPK model that can describe …
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Development of a PBPK-based health risk assessment framework for exposure to cerium, gold, silver and titanium engineered nanoparticles
… a novel risk assessment model framework. The PBPK study showed that the biodistribution of ceria nanoparticles is largely dependent on the exposure route and dose. The time courses for various tissues for intravenously (IV) administered 5 nm ceria were well articulated by the model. …
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Modeling approaches to characterize the disposition of monoclonal antibodies
… knowledge present in physiologically-based PK (PBPK) models is likely to support rational classical model selection and thus, a methodology to link empirical and PBPK models is desirable. However, published PBPK models for mAbs are quite diverse in respect to the physiology of distribution …
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First-principle based pharmacokinetic modeling
… 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 …
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Integrating nonlinear mixed effects and physiologically–based modeling approaches for the analysis of repeated measurement studies
… exploited in mechanistic physiological based PK (PBPK) modeling approaches -it is, however, ignored in the classical NLME modeling approach. Mechanistic physiological based models aim to incorporate relevant and known physiological processes which contribute to the overlying process of interest. …
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In vitro metabolism studies to inform physiologically-based pharmacokinetic modelling of mefloquine, ritonavir and proguanil
… use of physiologically based pharmacokinetic (PBPK) modelling. By combining in vitro data with available knowledge on the physicochemical properties of a drug PBPK modelling provides a mechanistic understanding of drug exposure. As such, the in vitro metabolic characteristics of 3 commonly used …
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Evaluation of Dose-Exposure-Response Relationships of Miltefosine and Discovery of Multicomponent Crystal Forms of Artesunate
… physiologically-based pharmacokinetic (PBPK) models to investigate the dose-exposure–response relationship of miltefosine in in silico clinical trials, with a particular focus on evaluating differences between children and adults. Furthermore, the study aimed to discover novel …
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Subcellular Fractionation Methods for the Quantification of Endogenous Protein in Human Liver Using Targeted Proteomics
… accurate physiological-based pharmacokinetic (PBPK) model, and the support for expression-activity correlations in clinical pharmacology studies. Different from traditional xenobiotic bioanalysis, human endogenous protein quantifications using targeted proteomics face many challenges, such as …
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Preclinical Pharmacology of the MDM2 Antagonist Nutlin-3a
… we used physiologically-based pharmacokinetic (PBPK) modeling to characterize the disposition of nutlin-3a in mice. Plasma protein binding and blood partitioning were assessed by in vitro studies. After intravenous (10 and 20 mg/kg) and oral (50, 100, and 200 mg/kg) dosing, tissue concentrations …
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In vitro and in silico profiling to assist pharmaceutical development
… a physiologically based pharmacokinetic (PBPK) modelling method was utilised to simulate the pharmacokinetic profiles of the same drugs. Interestingly both models produced satisfactory results for the solubility prediction of acidic drug and in the fed state however the solubility …
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Translational Pharmacokinetic-Pharmacodynamic Modeling and Simulation in the Development of Spectinamides, a Novel Class of Anti-Tuberculosis Agents
… <p>Physiologically-based pharmacokinetic (PBPK) modeling and simulation is a powerful methodology used in support of dose selection for first-in-human studies. The objective was to develop a PBPK model for describing pharmacokinetics of Lee 1599 in rats and mice, and to extrapolate this PK …
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Evaluation of different in vitro surrogates to represent nonspecific binding for tissue: plasma water partition coefficient predictions
… use of physiologically-based pharmacokinetic (PBPK) modeling to predict the pharmacokinetics of a drug, accurate prediction of the tissue: plasma water partition coefficients (Kp,m) has become increasingly important. In these predictions, drug-lipid interactions have been traditionally …
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Mechanistic modeling of alpha-synuclein aggregation and brain pharmacokinetics for drug development in neurodegeneration
… (QSP) and physiologically based pharmacokinetic (PBPK) modeling. The first part of the work focuses on the mathematical modeling of alpha-synuclein (aSyn) aggregation dynamics under in vitro conditions—a molecular process relevant to Parkinson’s disease (PD) and other synucleinopathies. Building …
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STATIC AND DYNAMIC FORMS TO IDENTIFY DDI POTENTIAL AND SOURCES OF PHARMACOKINETIC VARIABILITY
… using physiologically based pharmacokinetic (PBPK) modeling, and Specific Aim 3: to optimize clinical trial design to capture hydroxychloroquine 3-compartment pharmacokinetics by varying the sample size and sample collection timepoints in a population pharmacokinetic (PopPK) model. …
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Model-Guided Transdermal Formulation of 1α,25-Dihydroxyvitamin D3 for Improved Safety and Efficacy
… pharmacokinetic-pharmacodynamic (PBPK-PD) model was further established to interpret the complex PK and PD interplay of 1,25(OH)2D3 and guide dosing selection. Based on the modeling and studies in vivo, we were able to determine that patches containing loadings of 70-560 pmol‧cm-2 …
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Regulation of Human Renal Drug Transporters by Inflammatory Cytokines and Pregnancy-related Hormones in Primary Proximal Tubular Epithelial Cells
… into physiologically based pharmacokinetic (PBPK) models of inflammation, pregnancy, and their co-occurrence. The central hypothesis was that clinically relevant cytokine and hormone exposures cause coordinated, transporter-specific changes in mRNA expression and functional activity in human …
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An Affinity Threshold for Maximum Efficacy in Anti-PD-1 Cancer Immunotherapy
… a physiologically-based pharmacokinetic (PBPK) model to complement the in vivo results and highlight the direct relationship between dose, affinity, and PD-1 target saturation in the tumor. Through in vivo efficacy studies using the MC38 murine adenocarcinoma model, we found that there is …
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Computational Evaluation and Structure-based Design for Potentiation of Nicotine Vaccines
… applied physiologically-based pharmacokinetic (PBPK) modeling to better assess NV potential. Rat and human physiological and pharmacological parameters were obtained from literature and used to construct compartmentalized models for nicotine and cotinine distribution. These models were then …
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The Potential of Cellulose Nanocrystals in the Detection and Treatment of Cancer
… vivo, a physiologically based pharmacokinetic (PBPK) model has been constructed. We have also examined CNCs' ability to potentiate a new technique for tumor ablation, IRE. Pre-incubation with FA-conjugated CNCs (CNC-FA) have shown an increase in cytotoxicity in FR-positive cancer cells induced …
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Novel In-Vitro Approaches to Investigate Membrane Partitioning and pH-Dependent Passive Permeation of Small Molecule Drugs
… in permeability models and perfusion-limited PBPK models. Therefore, characterization of this early distribution phase by observing the time course of the free drug concentration in drug-spiked cell suspensions (MDCK & rat hepatocyte) was pursued with a novel in vitro microdialysis approach …
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