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Review
, 26 (3), 115-117

Mechanistic Ligand-Receptor Interaction Model: Operational Model of Agonism

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Review

Mechanistic Ligand-Receptor Interaction Model: Operational Model of Agonism

Hyungsub Kim et al. Transl Clin Pharmacol.

Abstract

This tutorial explains the basic principles of mechanistic ligand-receptor interaction model, which is an operational model of agonism. A growing number of agonist drugs, especially immune oncology drugs, is currently being developed. In this tutorial, time-dependent ordinary differential equation for simple Emax operational model of agonism was derived step by step. The differential equation could be applied in a pharmacodynamic modeling software, such as NONMEM, for use in non-steady state experiments, in which experimental data are generated while the interaction between ligand and receptor changes over time. Making the most of the non-steady state experimental data would simplify the experimental processes, and furthermore allow us to identify more detailed kinetics of a potential drug. The operational model of agonism could be useful to predict the optimal dose for agonistic drugs from in vitro and in vivo animal pharmacology experiments at the very early phase of drug development.

Keywords: Mechanistic ligand-receptor interaction; Operational model of agonism; Optimal dose; Prediction.

Conflict of interest statement

Conflicts of interests: Authors: The authors declare that they have no conflict of interests Reviewers: Nothing to declare Editors: Nothing to declare

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