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AFIR: A Dimensionless Potency Metric for Characterizing the Activity of Monoclonal Antibodies.

TitleAFIR: A Dimensionless Potency Metric for Characterizing the Activity of Monoclonal Antibodies.
Publication TypeJournal Article
Year of Publication2017
AuthorsStein AM, Ramakrishna R
JournalCPT Pharmacometrics Syst Pharmacol
Volume6
Issue4
Pagination258-266
Date Published2017 04
ISSN2163-8306
KeywordsAntibodies, Monoclonal, Dose-Response Relationship, Drug, Drug Dosage Calculations, Humans, Models, Biological, Molecular Targeted Therapy
Abstract

For monoclonal antibody (mAb) drugs, soluble targets may accumulate several thousand fold after binding to the drug. Time course data of mAb and total target is often collected and, although free target is more closely related to clinical effect, it is difficult to measure. Therefore, mathematical models of this data are used to predict target engagement. In this article, a "potency factor" is introduced as an approximation for the model-predicted target inhibition. This potency factor is defined to be the time-Averaged Free target concentration to Initial target concentration Ratio (AFIR), and it depends on three key quantities: the average drug concentration at steady state; the binding affinity; and the degree of target accumulation. AFIR provides the intuition for how changes in dosing regimen and binding affinity affect target capture and AFIR can be used to predict the druggability of new targets and the expected benefits of more potent, second-generation mAbs.

DOI10.1002/psp4.12169
Alternate JournalCPT Pharmacometrics Syst Pharmacol
PubMed ID28375563
PubMed Central IDPMC5397564