ArticleJournal of pharmacokinetics and pharmacodynamics2019
Two-pore physiologically based pharmacokinetic model with de novo derived parameters for predicting plasma PK of different size protein therapeutics.
Article in Journal of pharmacokinetics and pharmacodynamics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Physiologically based pharmacokinetic modeling of mRNA therapeutics: A multiscale framework for LNP and antibody trafficking in mice.Molecular therapy. Nucleic acids · 2026Article
- Differential expression of monoclonal antibody in rat brain following systemic and local administration of AAV.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Assessment of Telisotuzumab Vedotin Drug-Drug Interaction Potential Using Physiologically-Based Pharmacokinetic Modeling and Simulations.Journal of clinical pharmacology · 2025Article
- A multiscale physiologically based pharmacokinetic model to support mRNA-encoded BiTE therapy in cancer treatment.Molecular therapy. Nucleic acids · 2025Article
- A minimal physiologically-based pharmacokinetic modeling platform to predict intratumor exposure and receptor occupancy of an anti-LAG-3 monoclonal antibody.CPT: pharmacometrics & systems pharmacology · 2025Article
- A minimal physiologically based pharmacokinetic model to study the combined effect of antibody size, charge, and binding affinity to FcRn/antigen on antibody pharmacokinetics.Journal of pharmacokinetics and pharmacodynamics · 2024Article
- Translational two-pore PBPK model to characterize whole-body disposition of different-size endogenous and exogenous proteins.Journal of pharmacokinetics and pharmacodynamics · 2024Article
- Modeling onActa pharmaceutica Sinica. B · 2024Article
- A quantitative systems pharmacology (QSP) platform for preclinical to clinical translation ofFrontiers in pharmacology · 2024Article
- Physiologically based pharmacokinetic models for systemic disposition of protein therapeutics in rabbits.Frontiers in pharmacology · 2024Article
- Clinical validation of translational antibody PBPK model using tissue distribution data generated withJournal of pharmacokinetics and pharmacodynamics · 2023Article
- Physiologically Based Pharmacokinetic Modeling to Characterize the Effect of Molecular Charge on Whole-Body Disposition of Monoclonal Antibodies.The AAPS journal · 2023Article
- Monoclonal Antibody Pharmacokinetics in Cynomolgus Monkeys Following Subcutaneous Administration: Physiologically Based Model Predictions from Physiochemical Properties.The AAPS journal · 2022Article
- Physiologically-based pharmacokinetic model for pulmonary disposition of protein therapeutics in humans.Journal of pharmacokinetics and pharmacodynamics · 2022Article
- Leveraging a physiologically-based quantitative translational modeling platform for designing B cell maturation antigen-targeting bispecific T cell engagers for treatment of multiple myeloma.PLoS computational biology · 2022Article
- Mathematical Models to Characterize the Absorption, Distribution, Metabolism, and Excretion of Protein Therapeutics.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Recent Advances in Translational Pharmacokinetics and Pharmacodynamics Prediction of Therapeutic Antibodies Using Modeling and Simulation.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Two-pore physiologically based pharmacokinetic model validation using whole-body biodistribution of trastuzumab and different-size fragments in mice.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- A Two-Pore Physiologically Based Pharmacokinetic Model to Predict Subcutaneously Administered Different-Size Antibody/Antibody Fragments.The AAPS journal · 2021Article
- Development of a physiologically-based pharmacokinetic model for ocular disposition of monoclonal antibodies in rabbits.Journal of pharmacokinetics and pharmacodynamics · 2020Article
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Authors and funding
2 authors.
Funding
Abstract
Two-pore PBPK models have been used for characterizing the PK of protein therapeutics since 1990s. However, widespread utilization of these models is hampered by the lack of a priori parameter values, which are typically estimated using the observed data. To overcome this hurdle, here we have presented the development of a two-pore PBPK model using de novo derived parameters. The PBPK model was validated using plasma PK data for different size proteins in mice. Using the "two pore theory" we were able to establish the relationship between protein size and key model parameters, such as: permeability-surface area product (PS), vascular reflection coefficient (σ), peclet number (Pe), and glomerular sieving coefficient (θ). The model accounted for size dependent changes in tissue extravasation and glomerular filtration. The model was able to a priori predict the PK of 8 different proteins: IgG (150 kDa), scFv-Fc (105 kDa), F(ab)
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.