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

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

SUBMITTER: Stein AM 

PROVIDER: S-EPMC5397564 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature