ArticleJournal of pharmacokinetics and pharmacodynamics2016
Minimal physiologically-based pharmacokinetic (mPBPK) model for a monoclonal antibody against interleukin-6 in mice with collagen-induced arthritis.
Article in Journal of pharmacokinetics and pharmacodynamics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Modeling and Simulation of the Pharmacokinetics and Target Engagement of an Antagonist Monoclonal Antibody to Interferon-γ-Induced Protein 10, BMS-986184, in Healthy Participants to Guide Therapeutic Dosing.Clinical pharmacology in drug development · 2020Trial
- Review
- PBPK Modeling: Empowering Drug Development and Precision Dosing in China.CPT: pharmacometrics & systems pharmacology · 2025Review
- The Role of Pharmacometrics in Advancing the Therapies for Autoimmune Diseases.Pharmaceutics · 2024Review
- Local depletion of large molecule drugs due to target binding in tissue interstitial space.CPT: pharmacometrics & systems pharmacology · 2024Review
- Utility of Minimal Physiologically Based Pharmacokinetic Models for Assessing Fractional Distribution, Oral Absorption, and Series-Compartment Models of Hepatic Clearance.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Prediction of relative change in free nerve growth factor following subcutaneous administration of tanezumab, a novel monoclonal antibody to nerve growth factor.CPT: pharmacometrics & systems pharmacology · 2023Article
- A permeability- and perfusion-based PBPK model for improved prediction of concentration-time profiles.Clinical and translational science · 2022Article
- Recent Advances in Translational Pharmacokinetics and Pharmacodynamics Prediction of Therapeutic Antibodies Using Modeling and Simulation.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Minimal Physiologically-Based Pharmacokinetic (mPBPK) Metamodeling of Target Engagement in Skin Informs Anti-IL17A Drug Development in Psoriasis.Frontiers in pharmacology · 2022Article
- Modeling Pharmacokinetics and Pharmacodynamics of Therapeutic Antibodies: Progress, Challenges, and Future Directions.Pharmaceutics · 2021Review
- Expression and Correlation of IgG4 and IL-21 in Collagen-Induced Arthritis Rats.Journal of inflammation research · 2021Article
- Dose Correction for a Michaelis-Menten Approximation of a Target-Mediated Drug Disposition Model with a Multiple Intravenous Dosing Regimens.The AAPS journal · 2020Article
- Physiologically-Based Pharmacokinetic Modeling vs. Allometric Scaling for the Prediction of Infliximab Pharmacokinetics in Pediatric Patients.CPT: pharmacometrics & systems pharmacology · 2019Article
- Guiding dose selection of monoclonal antibodies using a new parameter (AFTIR) for characterizing ligand binding systems.Journal of pharmacokinetics and pharmacodynamics · 2019Article
- Physiologically-based modeling of monoclonal antibody pharmacokinetics in drug discovery and development.Drug metabolism and pharmacokinetics · 2019Review
- Role of Interstitial Fluid Turnover on Target Suppression by Therapeutic Biologics Using a Minimal Physiologically Based Pharmacokinetic Model.The Journal of pharmacology and experimental therapeutics · 2018Article
- A Minimal Physiologically Based Pharmacokinetic Model with a Nested Endosome Compartment for Novel Engineered Antibodies.The AAPS journal · 2018Article
- Interrelationships between Infliximab and Recombinant Tumor Necrosis Factor-Drug metabolism and disposition: the biological fate of chemicals · 2017Article
- Target-mediated drug disposition with drug-drug interaction, Part I: single drug case in alternative formulations.Journal of pharmacokinetics and pharmacodynamics · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Therapeutic monoclonal antibodies (mAb) targeting soluble inflammatory cytokines exert their pharmacological effects in rheumatoid arthritis through binding and neutralizing free cytokines in target tissue sites. Therefore suppression of free cytokines in such sites directly relates to the magnitude of therapeutic response. Although the interrelationships between mAb and cytokines have been examined in the systemic circulation, less is known about the interaction of mAb and cytokines in inflamed joints. In the present study, the interplay between the mAb, CNTO 345, and its target IL-6 in serum as well as ankle joint synovial fluid were characterized in collagen-induced arthritic mice. A minimal physiologically-based pharmacokinetic model with target-mediated drug disposition (TMDD) features in serum and ankle joint synovial fluid was developed for the assessment of the TMDD dynamics of CNTO 345 and IL-6. Our model indicates that TMDD kinetics in ankle joints differ greatly from that in serum. The differences can be attributed to the limited tissue distribution of CNTO 345 in ankle joint synovial fluid, the significant rise of the IL-6 baseline in ankle joint synovial fluid in comparison with serum, and the relative time-scales of elimination rates between CNTO 345, free IL-6 and CNTO 345-IL-6 complex in serum and ankle joint synovial fluid.
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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.