ArticleJournal of pharmacokinetics and pharmacodynamics2015
Development of a physiologically based pharmacokinetic model for a domain antibody in mice using the two-pore theory.
Article in Journal of pharmacokinetics and pharmacodynamics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- A pilot study evaluating GSK1070806 inhibition of interleukin-18 in renal transplant delayed graft function.PloS one · 2021Trial
- A new pharmacokinetic model forScientific reports · 2018Trial
- Integrating in vitro aerosol characterization and cross-species PBPK modeling to predict human lung exposure of inhaled therapeutic proteins.International journal of pharmaceutics: X · 2026Article
- PBPK Modelling of Antisense Oligonucleotide Therapeutics: Application for Predicting Plasma and Tissue Pharmacokinetics of Bepirovirsen.The AAPS journal · 2026Article
- Article
- A multiscale physiologically based pharmacokinetic model to support mRNA-encoded BiTE therapy in cancer treatment.Molecular therapy. Nucleic acids · 2025Article
- Cross-species translational modelling of targeted therapeutic oligonucleotides using physiologically based pharmacokinetics.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Accelerating Biologics PBPK Modelling with Automated Model Building: A Tutorial.Pharmaceutics · 2025Review
- Translational two-pore PBPK model to characterize whole-body disposition of different-size endogenous and exogenous proteins.Journal of pharmacokinetics and pharmacodynamics · 2024Article
- 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
- 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
- Predicting monoclonal antibody pharmacokinetics following subcutaneous administration via whole-body physiologically-based modeling.Journal of pharmacokinetics and pharmacodynamics · 2020Article
- Computer-assembled cross-species/cross-modalities two-pore physiologically based pharmacokinetic model for biologics in mice and rats.Journal of pharmacokinetics and pharmacodynamics · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Domain antibodies (dAbs) are the smallest antigen-binding fragments of immunoglobulins. To date, there is limited insight into the pharmacokinetics of dAbs, especially their distribution into tissues and elimination. The objective of this work was to develop a physiologically-based pharmacokinetic model to investigate the biodisposition of a non-specific dAb construct in mice. Following a single IV administration of 10 mg/kg dummy dAb protein to twenty four female mice, frequent blood samples were collected and whole body lateral sections were analyzed by quantitative whole-body autoradiography. The model is based on the two-pore hypothesis of extravasation where organ-specific isogravimetric flow rates (Jorg,ISO) and permeability-surface area products (PSorg) are expressed as linear functions of the lymph flow rate (Jorg) and the kidney compartment is modified to account for glomerular filtration of dAb. As a result, only Jorg, glomerular filtration coefficient and the combined volume of Bowman's capsule, proximal and distal renal tubules and loop of Henle were optimized by fitting simultaneously all blood and organ data to the model. Our model captures the pharmacokinetic profiles of dAb in blood and all organs and shows that extravasation into interstitial space is a predominantly diffusion-driven process. The parameter values were estimated with good precision (%RMSE ≈ 30) and low cross-correlation (R(2) < 0.2). We developed a flexible model with a limited parameter number that may be applied to other biotherapeutics after adapting for size-related effects on extravasation and renal elimination processes.
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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.