Target-Mediated Drug Disposition Model for Bispecific Antibodies: Properties, Approximation, and Optimal Dosing Strategy.

ABSTRACT: Bispecific antibodies (BsAbs) bind to two different targets, and create two binary and one ternary complex (TC). These molecules have shown promise as immuno-oncology drugs, and the TC is considered the pharmacologically active species that drives their pharmacodynamic effect. Here, we have presented a general target-mediated drug disposition (TMDD) model for these BsAbs, which bind to two different targets on different cell membranes. The model includes four different binding events for BsAbs, turnover of the targets, and internalization of the complexes. In addition, a quasi-equilibrium (QE) approximation with decreased number of binding parameters and, if necessary, reduced internalization parameters is presented. The model is further used to investigate the kinetics of BsAb and TC conc

SUBMITTER: Schropp J 

PROVIDER: S-EPMC6430159 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature