Local depletion of large molecule drugs due to target binding in tissue interstitial space.

ABSTRACT: Drug-target binding determines a drug's pharmacodynamics but can also have a profound impact on a drug's pharmacokinetics, known as target-mediated drug disposition (TMDD). TMDD models describe the influence of drug-target binding and target turnover on unbound drug concentrations and are frequently used for biologics and drugs with nonlinear plasma pharmacokinetics. For drug targets expressed in tissues, the effect of TMDD may not be detected when analyzing plasma concentration curves, but it might still affect tissue concentrations and occupancy. This review aimed to investigate the likeliness of such a scenario by reviewing the literature for a typical range of TMDD parameter values and their impact on local drug concentrations and target occupancy in a whole-body PBPK model with TMDD.

SUBMITTER: Zasedateleva T 

PROVIDER: S-EPMC11646940 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature