Investigating Impacts of Model Parameters Correlations in Global Sensitivity Analysis: Determining the Most Influential Parameters of a Minimal PBPK Model of Midazolam
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Authors: Linzhong Li
Development of Paclitaxel PBPK Model to Predict Tumour Concentration in Cancer Patients
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Integration of a Tumour Growth Inhibition Model within a Mouse Physiologically-Based Pharmacokinetic Model
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Application of Global Sensitivity Analysis Methods to Determine the Most Influential Parameters of a Minimal PBPK Model of Quinidine
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A Whole Body Physiologically-based Pharmacokinetic Model for Antibody Drug Conjugates—Model Development and Validation in Rat
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Mechanistic Modeling of Antibody Drug Conjugate Pharmacokinetics
Antibody Drug Conjugates (ADCs) are constructed by attaching a small molecule drug to an antibody via a linker. The antibody selectively targets tumor cells and releases the cytotoxic drug within the cells to kill cancerous cells while sparing healthy tissue. Although some ADCs have been approved, many unanswered questions remain, such as drug-drug interactions (DDIs) and […]
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PBPK Modeling & SimulationA Bottom-up Whole-body Physiologically-based Pharmacokinetic Model to Mechanistically Predict Tissue Distribution and the Rate of Subcutaneous Absorption of Therapeutic Proteins
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A Mechanistic Minimal PBPK Model to Predict Distribution and Subcutaneous Absorption of Therapeutic Proteins
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A Minimal Physiologically-based Pharmacokinetic Model of IgG: Impact of Inclusion of 2:1 FcRn IgG Binding Stoichiometry and a Proportion of CL That Is Independent of FcRn Binding
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Emerging Covariates on the Pharmacokinetics of Monoclonal Antibodies: Do Current PBPK Models Account for the Significant Covariates Identified in PopPK Studies?
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Prediction of the Pharmacokinetics, Pharmacodynamics, and Efficacy of a Monoclonal Antibody, Using a Physiologically-based Pharmacokinetic FcRn Model
Although advantages of physiologically based pharmacokinetic models (PBPK) are now well established, PBPK models that are linked to pharmacodynamic (PD) models to predict pharmacokinetics (PK), PD, and efficacy of monoclonal antibodies (mAbs) in humans are uncommon. The aim of this study was to develop a PD model that could be linked to a physiologically based mechanistic FcRn model to predict PK, PD, and efficacy of efalizumab. The mechanistic FcRn model for mAbs with target-mediated drug disposition within […]
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A Mechanistic PBPK Model to Predict Subcutaneous Absorption of Therapeutic Proteins and Monoclonal Antibodies
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Modeling the Binding Kinetics of Antibody, Antigen, and FcyRs
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Simulation of Monoclonal Antibody Pharmacokinetics in Humans Using a Minimal Physiologically-based Model
Compared to small chemical molecules, antibodies and Fc-containing derivatives (mAbs) have unique pharmacokinetic behavior characterized by relatively poor cellular permeability, minimal renal filtration, binding to FcRn, target-mediated drug disposition, and disposition via lymph. A minimal physiologically based pharmacokinetic (PBPK) model to describe the pharmacokinetics of mAbs in humans was developed. Within the model, the body is divided into three physiological compartments; plasma, a single tissue compartment and lymph. The […]
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Exploring Fixed Dose versus Body Weight-based Dosing for Monoclonal Antibodies Using Physiologically-based Pharmacokinetic Modeling
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A Mechanistic Model to Predict Subcutaneous Absorption of Therapeutic Proteins Linked to a Whole Body PBPK Model
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A Semi-mechanistic Model to Predict Renal Clearance of Therapeutic Proteins Linked to a Whole Body PBPK Model
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Modeling the Binding Kinetics of Bispecific Antibodies under the Framework of a Minimal Human PBPK Model
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Incorporating Target Shedding into a Minimal PBPK-TMDD Model for Monoclonal Antibodies
Shedding of a pharmacological target from cells, giving rise to a soluble target that can also bind therapeutic proteins, is a common phenomenon. In this study, a minimal physiologically based pharmacokinetic model was used to simulate the pharmacokinetics of trastuzumab and the simultaneous binding of the compound to soluble (in blood and tissue interstitial space) and membrane-bound (in the tissue interstitial space) forms of […]
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Use of a Minimal PBPK Model to Investigate the Effect of Shed Antigen on Simulated Trastuzumab in Humans
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