ArticleThe AAPS journal2012
Evaluation of a catenary PBPK model for predicting the in vivo disposition of mAbs engineered for high-affinity binding to FcRn.
Article in The AAPS journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 102 citations in OpenAlex.
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- Enhanced Clearance of HIV-1 Broadly Neutralizing Antibody VRC07-523-LS During Viremia: Influences on Trial Design and Analysis.Clinical and translational science · 2026Article
- Physiologically Based Pharmacokinetic Models for Infliximab, Ipilimumab, and Nivolumab Developed with GastroPlus to Predict Hepatic Concentrations.Pharmaceutics · 2025Article
- Enhanced and sustained biodistribution of HIV-1 neutralizing antibody VRC01LS in human genital and rectal mucosa.Nature communications · 2024Article
- Kinetics of RPR Decline in Pregnant Persons Treated for Syphilis in Pregnancy and Their Infants.Pathogens (Basel, Switzerland) · 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
- Translational two-pore PBPK model to characterize whole-body disposition of different-size endogenous and exogenous proteins.Journal of pharmacokinetics and pharmacodynamics · 2024Article
- Physiologically based pharmacokinetic models for systemic disposition of protein therapeutics in rabbits.Frontiers in pharmacology · 2024Article
- Kinetic modeling of the plasma pharmacokinetic profiles of ADAMTS13 fragment and its Fc-fusion counterpart in mice.Frontiers in pharmacology · 2024Article
- Article
- Physiologically Based Pharmacokinetic Modeling to Characterize the Effect of Molecular Charge on Whole-Body Disposition of Monoclonal Antibodies.The AAPS journal · 2023Article
- Review of the Existing Translational Pharmacokinetics Modeling Approaches Specific to Monoclonal Antibodies (mAbs) to Support the First-In-Human (FIH) Dose Selection.International journal of molecular sciences · 2022Review
- 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
- Pharmacokinetic-pharmacodynamic modelling of the anti-FcRn monoclonal antibody rozanolixizumab: Translation from preclinical stages to the clinic.CPT: pharmacometrics & systems pharmacology · 2022Article
- Minimal brain PBPK model to support the preclinical and clinical development of antibody therapeutics for CNS diseases.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- Current and prospective computational approaches and challenges for developing COVID-19 vaccines.Advanced drug delivery reviews · 2021Review
- Modeling Pharmacokinetics and Pharmacodynamics of Therapeutic Antibodies: Progress, Challenges, and Future Directions.Pharmaceutics · 2021Review
- In Translation: FcRn across the Therapeutic Spectrum.International journal of molecular sciences · 2021Review
- Development of a Pharmacokinetic Model Describing Neonatal Fc Receptor-Mediated Recycling of HL2351, a Novel Hybrid Fc-Fused Interleukin-1 Receptor Antagonist, to Optimize Dosage Regimen.CPT: pharmacometrics & systems pharmacology · 2020Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Efforts have been made to extend the biological half-life of monoclonal antibody drugs (mAbs) by increasing the affinity of mAb-neonatal Fc receptor (FcRn) binding; however, mixed results have been reported. One possible reason for a poor correlation between the equilibrium affinity of mAb-FcRn binding and mAb systemic pharmacokinetics is that the timecourse of endosomal transit is too brief to allow binding to reach equilibrium. In the present work, a new physiologically based pharmacokinetic (PBPK) model has been developed to approximate the pH and time-dependent endosomal trafficking of immunoglobulin G (IgG). In this model, a catenary sub-model was utilized to describe the endosomal transit of IgG and the time dependencies in IgG-FcRn association and dissociation. The model performs as well as a previously published PBPK model, with assumed equilibrium kinetics of mAb-FcRn binding, in capturing the disposition profile of murine mAb from wild-type and FcRn knockout mice (catenary vs. equilibrium model: r (2), 0.971 vs. 0.978; median prediction error, 3.38% vs. 3.79%). Compared to the PBPK model with equilibrium binding, the present catenary PBPK model predicts much more moderate changes in half-life with altered FcRn binding. For example, for a 10-fold increase in binding affinity, the catenary model predicts <2.5-fold change in half-life compared to an ∼8-fold increase as predicted by the equilibrium model; for a 100-fold increase in binding affinity, the catenary model predicts ∼7-fold change in half-life compared to >70-fold increase as predicted by the equilibrium model. Predictions of the new catenary PBPK model are more consistent with experimental results in the published literature.
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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.