Mechanistic ligand-receptor interaction model: operational model of agonism
10.12793/tcp.2018.26.3.115
- Author:
Hyungsub KIM
1
;
Hyeong Seok LIM
Author Information
1. Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan, Seoul 05505, Republic of Korea. mdlhs@amc.seoul.kr
- Publication Type:Review
- Keywords:
Mechanistic ligand-receptor interaction;
Operational model of agonism;
Optimal dose;
Prediction
- MeSH:
Animals;
Felodipine;
In Vitro Techniques;
Kinetics;
Pharmacology
- From:Translational and Clinical Pharmacology
2018;26(3):115-117
- CountryRepublic of Korea
- Language:English
-
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 E(max) 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.
