ArticleJournal of pharmacokinetics and pharmacodynamics2012
Methods of solving rapid binding target-mediated drug disposition model for two drugs competing for the same receptor.
Article in Journal of pharmacokinetics and pharmacodynamics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Exact Formula of the Total Quasi-Steady State Approximation in Competitive Target-Mediated Drug Disposition.Computational and structural biotechnology journal · 2026Article
- General quasi-equilibrium multivalent binding model to study diverse and complex drug-receptor interactions of biologics.Journal of pharmacokinetics and pharmacodynamics · 2024Article
- Optimizing Clinical Translation of Bispecific T-cell Engagers through Context Unification with a Quantitative Systems Pharmacology Model.Clinical pharmacology and therapeutics · 2024Article
- Article
- The quest for balance between capturing data and model complexity: A quantitative clinical pharmacology approach applied to monoclonal antibodies.CPT: pharmacometrics & systems pharmacology · 2023Article
- Algorithmic multiscale analysis for the FcRn mediated regulation of antibody PK in human.Scientific reports · 2022Article
- Estimating drug potency in the competitive target mediated drug disposition (TMDD) system when the endogenous ligand is included.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- Simultaneous Target-Mediated Drug Disposition Model for Two Small-Molecule Compounds Competing for Their Pharmacological Target: Soluble Epoxide Hydrolase.The Journal of pharmacology and experimental therapeutics · 2020Article
- A physiological model of granulopoiesis to predict clinical drug induced neutropenia from in vitro bone marrow studies: with application to a cell cycle inhibitor.Journal of pharmacokinetics and pharmacodynamics · 2020Article
- Population pharmacokinetics and covariate analysis of Sym004, an antibody mixture against the epidermal growth factor receptor, in subjects with metastatic colorectal cancer and other solid tumors.Journal of pharmacokinetics and pharmacodynamics · 2020Article
- Parameter Identification for a Model of Neonatal Fc Receptor-Mediated Recycling of Endogenous Immunoglobulin G in Humans.Frontiers in immunology · 2019Article
- New Equilibrium Models of Drug-Receptor Interactions Derived from Target-Mediated Drug Disposition.The AAPS journal · 2018Article
- Target-Mediated Drug Disposition Pharmacokinetic-Pharmacodynamic Model of Bosentan and Endothelin-1.Clinical pharmacokinetics · 2017Article
- AFIR: A Dimensionless Potency Metric for Characterizing the Activity of Monoclonal Antibodies.CPT: pharmacometrics & systems pharmacology · 2017Article
- Target mediated drug disposition with drug-drug interaction, Part II: competitive and uncompetitive cases.Journal of pharmacokinetics and pharmacodynamics · 2017Article
- Target-mediated drug disposition with drug-drug interaction, Part I: single drug case in alternative formulations.Journal of pharmacokinetics and pharmacodynamics · 2017Article
- Analysis of a Compartmental Model of Endogenous Immunoglobulin G Metabolism with Application to Multiple Myeloma.Frontiers in physiology · 2017Article
- Assessment of non-linear combination effect terms for drug-drug interactions.Journal of pharmacokinetics and pharmacodynamics · 2016Review
- Mechanism-Based Competitive Binding Model to Investigate the Effect of Neonatal Fc Receptor Binding Affinity on the Pharmacokinetic of Humanized Anti-VEGF Monoclonal IgG1 Antibody in Cynomolgus Monkey.The AAPS journal · 2016Article
- Pharmacodynamic model for chemoradiotherapy-induced thrombocytopenia in mice.Journal of pharmacokinetics and pharmacodynamics · 2015Article
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Funding
Abstract
The target-mediated drug disposition (TMDD) model has been adopted to describe pharmacokinetics for two drugs competing for the same receptor. A rapid binding assumption introduces total receptor and total drug concentrations while free drug concentrations C (A) and C (B) are calculated from the equilibrium (Gaddum) equations. The Gaddum equations are polynomials in C (A) and C (B) of second degree that have explicit solutions involving complex numbers. The aim of this study was to develop numerical methods to solve the rapid binding TMDD model for two drugs competing for the same receptor that can be implemented in pharmacokinetic software. Algebra, calculus, and computer simulations were used to develop algorithms and investigate properties of solutions to the TMDD model with two drugs competitively binding to the same receptor. A general rapid binding approximation of the TMDD model for two drugs competing for the same receptor has been proposed. The explicit solutions to the equilibrium equations employ complex numbers, which cannot be easily solved by pharmacokinetic software. Numerical bisection algorithm and differential representation were developed to solve the system instead of obtaining an explicit solution. The numerical solutions were validated by MATLAB 7.2 solver for polynomial roots. The applicability of these algorithms was demonstrated by simulating concentration-time profiles resulting from exogenous and endogenous IgG competing for the neonatal Fc receptor (FcRn), and darbepoetin competing with endogenous erythropoietin for the erythropoietin receptor. These models were implemented in ADAPT 5 and Phoenix WinNonlin 6.0, respectively.
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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.