Translation of Monoclonal Antibodies Pharmacokinetics from Animal to Human Using Physiologically Based Modeling in Open Systems Pharmacology (OSP) Suite: A Retrospective Analysis of Bevacizumab.

ABSTRACT: Interspecies translation of monoclonal antibodies (mAbs) pharmacokinetics (PK) in presence of target-mediated drug disposition (TMDD) is particularly challenging. Incorporation of TMDD in physiologically based PK (PBPK) modeling is recent and needs to be consolidated and generalized to provide better prediction of TMDD regarding inter-species translation during preclinical and clinical development steps of mAbs. The objective of this study was to develop a generic PBPK translational approach for mAbs using the open-source software (PK-Sim^® and Mobi^®). The translation of bevacizumab based on data in non-human primates (NHP), healthy volunteers (HV), and cancer patients was used as a case example for model demonstration purpose. A PBPK model for bevacizumab concentratio

SUBMITTER: Pasquiers B 

PROVIDER: S-EPMC10459442 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature