Journal: Drug Metabolism and Disposition

Article Title: Toxicokinetics and Physiologically Based Pharmacokinetic Modeling of the Shellfish Toxin Domoic Acid in Nonhuman Primates

doi: 10.1124/dmd.117.078485

Figure Lengend Snippet: Summary of input parameter values for DA PBPK model in monkeys

Article Snippet: A PBPK model of DA disposition in humans was constructed as a full PBPK model using Simcyp version 16 (Certara).

Techniques: Molecular Weight

Journal: Drug Metabolism and Disposition

Article Title: Toxicokinetics and Physiologically Based Pharmacokinetic Modeling of the Shellfish Toxin Domoic Acid in Nonhuman Primates

doi: 10.1124/dmd.117.078485

Figure Lengend Snippet: Observed and predicted toxicokinetic parameters of DA in monkeys after single intravenous doses Observed values are reported as geometric mean ± S.D. The predicted population representative values simulated using the PBPK model are shown together with the predicted range of values included in parentheses.

Article Snippet: A PBPK model of DA disposition in humans was constructed as a full PBPK model using Simcyp version 16 (Certara).

Techniques:

Journal: Drug Metabolism and Disposition

Article Title: Toxicokinetics and Physiologically Based Pharmacokinetic Modeling of the Shellfish Toxin Domoic Acid in Nonhuman Primates

doi: 10.1124/dmd.117.078485

Figure Lengend Snippet: Observed and predicted toxicokinetic parameters of DA in monkeys after single oral doses Observed values are reported as geometric mean ± S.D except for C max which is the arithmetic mean and S.D. The predicted population representative value simulated using the PBPK model is shown together with the predicted range of values included in parentheses.

Article Snippet: A PBPK model of DA disposition in humans was constructed as a full PBPK model using Simcyp version 16 (Certara).

Techniques:

Journal: CPT: Pharmacometrics & Systems Pharmacology

Article Title: Physiologically‐based pharmacokinetic pharmacodynamic parent‐metabolite model of edoxaban to predict drug–drug‐disease interactions: M4 contribution

doi: 10.1002/psp4.12977

Figure Lengend Snippet: Parameter‐values used for PBPK/PD models of edoxaban and M4 in SimCYP.

Article Snippet: A whole‐body PBPK model with a linear additive PD model of edoxaban and its active metabolite M4 was developed and validated in SimCYP for healthy adults with or without interacting drugs.

Techniques: Binding Assay, Molecular Weight

Journal: CPT: Pharmacometrics & Systems Pharmacology

Article Title: Physiologically‐based pharmacokinetic pharmacodynamic parent‐metabolite model of edoxaban to predict drug–drug‐disease interactions: M4 contribution

doi: 10.1002/psp4.12977

Figure Lengend Snippet: Prediction of the pharmacokinetic (PK) profiles for edoxaban and M4 at a series of doses in healthy subjects using physiologically‐based PK modeling. Simulation (mean predictions in black lines and 5th–95th percentiles of predictions in gray shade) of PK profiles was conducted for a single i.v. dose of 30 mg, a single oral dose of 10, 30, 60, 90, 120, and 150 mg and multiple oral doses of 60 mg edoxaban (log scale was on the right top in each dose panel).

Article Snippet: A whole‐body PBPK model with a linear additive PD model of edoxaban and its active metabolite M4 was developed and validated in SimCYP for healthy adults with or without interacting drugs.

Techniques:

Journal: CPT: Pharmacometrics & Systems Pharmacology

Article Title: Physiologically‐based pharmacokinetic pharmacodynamic parent‐metabolite model of edoxaban to predict drug–drug‐disease interactions: M4 contribution

doi: 10.1002/psp4.12977

Figure Lengend Snippet: Global sensitivity analysis of absorption, distribution, metabolism, and excretion parameters of edoxaban and M4 on AUC of edoxaban (a), area under the curve (AUC) of M4 (b) and AUC of anticoagulation pharmacodynamic response (c). μ*: The average of absolute elementary effects. CL int , intrinsic clearance; J max , maximal flux value; Peff, effective permeability.

Article Snippet: A whole‐body PBPK model with a linear additive PD model of edoxaban and its active metabolite M4 was developed and validated in SimCYP for healthy adults with or without interacting drugs.

Techniques: Permeability

Journal: CPT: Pharmacometrics & Systems Pharmacology

Article Title: Is the GFR‐based scaling approach adequate for predicting pediatric renal clearance of drugs with passive tubular reabsorption? Insights from PBPK modeling

doi: 10.1002/psp4.13254

Figure Lengend Snippet: Input data and model parameters for final metronidazole PBPK model in adults.

Article Snippet: The dose fraction for each metabolic or excretion pathway was determined based on the mass balance in vivo study of metronidazole in healthy adults., An adult intravenous PBPK model of metronidazole was initially developed using Simcyp (Version 22) and verified with clinical adult data.

Techniques: Clinical Proteomics, Binding Assay, Molecular Weight, Concentration Assay

Journal: CPT: Pharmacometrics & Systems Pharmacology

Article Title: Is the GFR‐based scaling approach adequate for predicting pediatric renal clearance of drugs with passive tubular reabsorption? Insights from PBPK modeling

doi: 10.1002/psp4.13254

Figure Lengend Snippet: Observed versus predicted plasma concentration‐time profiles by Pediatric Model II of metronidazole in pediatrics following different intravenous dosing regimens of metronidazole in Cohen et al. study. The orange dots represent individual‐level observations. The blue and gray lines represent the predicted mean and 90% prediction interval of simulated plasma concentration‐time profiles by Pediatric Model I. Literature data sources are presented in Table .

Article Snippet: The dose fraction for each metabolic or excretion pathway was determined based on the mass balance in vivo study of metronidazole in healthy adults., An adult intravenous PBPK model of metronidazole was initially developed using Simcyp (Version 22) and verified with clinical adult data.

Techniques: Clinical Proteomics, Concentration Assay

Journal: PLoS ONE

Article Title: A Liver-Centric Multiscale Modeling Framework for Xenobiotics

doi: 10.1371/journal.pone.0162428

Figure Lengend Snippet: Whole body uptake, distribution and clearance (1a) is represented as a PBPK model (1b) in SBML. The rectangular compartments represent tissues or blood compartments with blood flows between compartments indicated by black arrows. The compartment labeled “Rest” is the remainder of the body. The blue arrows and ovals represent non-blood borne transfer between compartments and organ lumens or, in the case of liver metabolism, an unspecified location external to the PBPK model. The tissue scale model of the liver (2a) is represented in CC3D as a single sinusoid modeled as a linear pipe lined with hepatocytes (green) (2b). Blood flow within the sinusoid consists of RBCs (red) and portions of serum (blue). Portions of serum are modeled as generalized cells. The hepatocyte (3a) metabolic pathways (3b) are model as a set of chemical reactions expressed in SBML.

Article Snippet: This whole-body PBPK model has been deposited in the BioModels Database [ ] ( http://www.ebi.ac.uk/biomodels-main/ ) as MODEL1509230010.

Techniques: Labeling

Journal: PLoS ONE

Article Title: A Liver-Centric Multiscale Modeling Framework for Xenobiotics

doi: 10.1371/journal.pone.0162428

Figure Lengend Snippet: Whole-body PBPK Model Rate Equations.

Article Snippet: This whole-body PBPK model has been deposited in the BioModels Database [ ] ( http://www.ebi.ac.uk/biomodels-main/ ) as MODEL1509230010.

Techniques:

Journal: PLoS ONE

Article Title: A Liver-Centric Multiscale Modeling Framework for Xenobiotics

doi: 10.1371/journal.pone.0162428

Figure Lengend Snippet: PBPK Parameter Set REFSIM.

Article Snippet: This whole-body PBPK model has been deposited in the BioModels Database [ ] ( http://www.ebi.ac.uk/biomodels-main/ ) as MODEL1509230010.

Techniques: Clinical Proteomics, Binding Assay, Filtration

Journal: PLoS ONE

Article Title: A Liver-Centric Multiscale Modeling Framework for Xenobiotics

doi: 10.1371/journal.pone.0162428

Figure Lengend Snippet: CC3D Parameters.

Article Snippet: This whole-body PBPK model has been deposited in the BioModels Database [ ] ( http://www.ebi.ac.uk/biomodels-main/ ) as MODEL1509230010.

Techniques: Diffusion-based Assay, Concentration Assay

Journal: PLoS ONE

Article Title: A Liver-Centric Multiscale Modeling Framework for Xenobiotics

doi: 10.1371/journal.pone.0162428

Figure Lengend Snippet: The horizontal axis lists the model’s parameters grouped by the sub-model. Parameters for the PBPK model start with “pbpk_”, the sinusoid models with “cc3d_” and the subcellular model with “sc_”. The vertical axis lists the model’s outputs duplicated for each of the input parameter sets. The “Average” row is the average of all the sensitivities in the column for the particular parameter set. Each square in the heat map is the relative change of a model output divided by the relative change of the model parameter in single-parameter-variation simulation. Dark space indicates little influence of a parameter on the model outputs, bright regions reflect strong influence of a parameter and white regions represent sensitivities greater than one.

Article Snippet: This whole-body PBPK model has been deposited in the BioModels Database [ ] ( http://www.ebi.ac.uk/biomodels-main/ ) as MODEL1509230010.

Techniques:

Journal: PLoS ONE

Article Title: A Liver-Centric Multiscale Modeling Framework for Xenobiotics

doi: 10.1371/journal.pone.0162428

Figure Lengend Snippet: Comparison of the sensitivities for the compound-independent parameters in the whole-body PBPK model about the fixed point REFSIM . Axis are as described in .

Article Snippet: This whole-body PBPK model has been deposited in the BioModels Database [ ] ( http://www.ebi.ac.uk/biomodels-main/ ) as MODEL1509230010.

Techniques: Comparison