ArticleJournal of pharmacokinetics and pharmacodynamics2015
Simulations of site-specific target-mediated pharmacokinetic models for guiding the development of bispecific antibodies.
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 13 papers.
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Who cites it
13 citing papers in PubMed, 29 citations in OpenAlex.
- General quasi-equilibrium multivalent binding model to study diverse and complex drug-receptor interactions of biologics.Journal of pharmacokinetics and pharmacodynamics · 2024Article
- Mechanistic computational modeling of monospecific and bispecific antibodies targeting interleukin-6/8 receptors.PLoS computational biology · 2024Article
- Minimally sufficient experimental design using identifiability analysis.NPJ systems biology and applications · 2024Article
- A Bispecific Modeling Framework Enables the Prediction of Efficacy, Toxicity, and Optimal Molecular Design of Bispecific Antibodies Targeting MerTK.The AAPS journal · 2024Article
- Article
- Identifying Safety Thresholds for Immunosuppressive Drugs: Applying Insights from Primary Antibody Deficiencies to Mitigate Adverse Events in Secondary Antibody Deficiencies Using Mathematical Modeling of Preclinical and Early Clinical Data.European journal of drug metabolism and pharmacokinetics · 2021Review
- Article
- Target-Mediated Drug Disposition Model for Bispecific Antibodies: Properties, Approximation, and Optimal Dosing Strategy.CPT: pharmacometrics & systems pharmacology · 2019Article
- A pre-clinical quantitative model predicts the pharmacokinetics/pharmacodynamics of an anti-BDCA2 monoclonal antibody in humans.Journal of pharmacokinetics and pharmacodynamics · 2018Article
- Comparison of tenofovir plasma and tissue exposure using a population pharmacokinetic model and bootstrap: a simulation study from observed data.Journal of pharmacokinetics and pharmacodynamics · 2017Article
- Assessing the Impact of Tissue Target Concentration Data on Uncertainty in In Vivo Target Coverage Predictions.CPT: pharmacometrics & systems pharmacology · 2016Article
- The application of mathematical modelling to the design of bispecific monoclonal antibodies.mAbs · 2016Article
- Pharmacokinetic and pharmacodynamic considerations for the next generation protein therapeutics.Journal of pharmacokinetics and pharmacodynamics · 2015Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bispecific antibodies (BAbs) are novel constructs that are under development and show promise as new therapeutic modalities for cancer and autoimmune disorders. The aim of this study is to develop a semi-mechanistic modeling approach to elucidate the disposition of BAbs in plasma and possible sites of action in humans. Here we present two case studies that showcase the use of modeling to guide BAb development. In case one, a BAb is directed against a soluble and a membrane-bound ligand for treating systemic lupus erythematosus, and in case two, a BAb targets two soluble ligands as a potential treatment for ulcerative colitis and asthma. Model simulations revealed important differences between plasma and tissues, when evaluated for drug disposition and target suppression. Target concentrations at tissue sites and type (soluble vs membrane-bound), tissue-site binding, and binding affinity are all major determinants of BAb disposition and subsequently target suppression. For the presented case studies, higher doses and/or frequent dosing regimens are required to achieve 80 % target suppression in site specific tissue (the more relevant matrix) as compared to plasma. Site-specific target-mediated models may serve to guide the selection of first-in-human doses for new BAbs.
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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.