ArticleThe AAPS journal2014
Simplification of complex physiologically based pharmacokinetic models of monoclonal antibodies.
Article in The AAPS journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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
6 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation Approaches: A Systematic Review of Published Models, Applications, and Model Verification.Drug metabolism and disposition: the biological fate of chemicals · 2015Pooled it
- Improving priors for human monoclonal antibody linear pharmacokinetic parameters by using half-lives from non-human primates.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- MPBPK-TMDD models for mAbs: alternative models, comparison, and identifiability issues.Journal of pharmacokinetics and pharmacodynamics · 2018Article
- Understanding the Monoclonal Antibody Disposition after Subcutaneous Administration using a Minimal Physiologically based Pharmacokinetic Model.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2018Article
- Potential Sources of Inter-Subject Variability in Monoclonal Antibody Pharmacokinetics.Clinical pharmacokinetics · 2016Review
- An Extended Minimal Physiologically Based Pharmacokinetic Model: Evaluation of Type II Diabetes Mellitus and Diabetic Nephropathy on Human IgG Pharmacokinetics in Rats.The AAPS journal · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
Monoclonal antibodies (mAbs) exhibit biexponential profiles in plasma that are commonly described with a standard two-compartment model with elimination from the central compartment. These models adequately describe mAb plasma PK. However, these models ignore elimination from the peripheral compartment. This may lead to underestimation of the volume of distribution of the peripheral compartment and thus over-predicts concentration in the peripheral compartment. We developed a simple and physiologically relevant model that incorporates information on binding and dissociation rates between mAb and FcRn receptor, mAb uptake, reflection, and catabolic degradation. We employed a previously published PBPK model and, with assumptions regarding rates of processes controlling mAb disposition, reduced the complex PBPK model to a simpler circular model with central, peripheral, and lymph compartments specifying elimination from both central and peripheral. We successfully applied the model to describe the PK of an investigational mAb. Our model presents an improvement over standard two-compartmental models in predicting whole-body average tissue concentrations while adequately describing plasma PK with minimal complexity and physiologically more meaningful parameters.
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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.