Properties of a general PK/PD model of antibody-ligand interactions for therapeutic antibodies that bind to soluble endogenous targets.
Antibodies that target endogenous soluble ligands are an important class of biotherapeutic agents. While much focus has been placed on characterization of antibody pharmacokinetics, less emphasis has been given to characterization of antibody effects on their soluble targets. We describe here the properties of a generalized mechanism-based PK/PD model used to characterize the in vivo interaction of an antibody and an endogenous soluble ligand. The assumptions and properties of the model are explored, and situations are described when deviations from the basic assumptions may be necessary. This model is most useful for in vivo situations where both antibody and ligand levels are available following drug administration. For a given antibody exposure, the extent and duration of suppression of free ligand is impacted by the apparent affinity of the interaction, as well as by the rate of ligand turnover. The applicability of the general equilibrium model of in vivo antibody-ligand interaction is demonstrated with an anti-Aß antibody.
Davda
Jasmine P
JP
Eli Lilly and Company, Drug Disposition, Lilly Corporate Center, Indianapolis, IN, USA.
Hansen
Ryan J
RJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D003198:Computer Simulation; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008954:Models, Biological; D011485:Protein Binding; D013997:Time Factors
D000911:Antibodies, Monoclonal; D008024:Ligands