ArticleThe AAPS journal2017
Pharmacokinetic Steady-States Highlight Interesting Target-Mediated Disposition Properties.
Article in The AAPS journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Lack of Differences in the Pharmacokinetics of Therapeutic Monoclonal Antibodies Between Japanese and Non-Japanese Individuals.Journal of clinical pharmacology · 2026Review
- Local depletion of large molecule drugs due to target binding in tissue interstitial space.CPT: pharmacometrics & systems pharmacology · 2024Review
- The quest for balance between capturing data and model complexity: A quantitative clinical pharmacology approach applied to monoclonal antibodies.CPT: pharmacometrics & systems pharmacology · 2023Article
- Estimating drug potency in the competitive target mediated drug disposition (TMDD) system when the endogenous ligand is included.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- Does In Vitro Potency Predict Clinically Efficacious Concentrations?Clinical pharmacology and therapeutics · 2020Article
- Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Dupilumab in Healthy Adult Subjects.Clinical pharmacology in drug development · 2020Article
- Interpretation of Drug Interaction Using Systemic and Local Tissue Exposure Changes.Pharmaceutics · 2020Review
- Guiding dose selection of monoclonal antibodies using a new parameter (AFTIR) for characterizing ligand binding systems.Journal of pharmacokinetics and pharmacodynamics · 2019Article
- Challenge model of TNFJournal of pharmacokinetics and pharmacodynamics · 2019Article
- The computation of biomarkers in pharmacokinetics with the aid of singular perturbation methods.Journal of mathematical biology · 2018Article
- Michaelis-Menten from an In Vivo Perspective: Open Versus Closed Systems.The AAPS journal · 2018Article
- New Equilibrium Models of Drug-Receptor Interactions Derived from Target-Mediated Drug Disposition.The AAPS journal · 2018Article
- Impact of target interactions on small-molecule drug disposition: an overlooked area.Nature reviews. Drug discovery · 2018Article
- Impact of mathematical pharmacology on practice and theory: four case studies.Journal of pharmacokinetics and pharmacodynamics · 2018Article
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Authors and funding
2 authors.
Funding
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Abstract
In this paper, we derive explicit expressions for the concentrations of ligand L, target R and ligand-target complex RL at steady state for the classical model describing target-mediated drug disposition, in the presence of a constant-rate infusion of ligand. We demonstrate that graphing the steady-state values of ligand, target and ligand-target complex, we obtain striking and often singular patterns, which yield a great deal of insight and understanding about the underlying processes. Deriving explicit expressions for the dependence of L, R and RL on the infusion rate, and displaying graphs of the relations between L, R and RL, we give qualitative and quantitive information for the experimentalist about the processes involved. Understanding target turnover is pivotal for optimising these processes when target-mediated drug disposition (TMDD) prevails. By a combination of mathematical analysis and simulations, we also show that the evolution of the three concentration profiles towards their respective steady-states can be quite complex, especially for lower infusion rates. We also show how parameter estimates obtained from iv bolus studies can be used to derive steady-state concentrations of ligand, target and complex. The latter may serve as a template for future experimental designs.
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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.