A translational physiologically-based pharmacokinetic model for MMAE-based antibody-drug conjugates.

ABSTRACT: The objective of this work was to develop a translational physiologically-based pharmacokinetic (PBPK) model for antibody-drug conjugates (ADCs), using monomethyl auristatin E (MMAE)-based ADCs. A previously established dual-structured whole-body PBPK model for MMAE-based ADCs in mice was scaled to higher species (i.e., rats and monkeys) and humans. Species-specific physiological and drug-related parameters for the payload and antibody backbone of ADCs were obtained from literature. Parameters associated with payload release, including the deconjugation rate, were optimized using an allometric scaling approach, and antibody degradation rate was adjusted to account for the enhanced clearance of ADCs due to conjugation across different species. The translational PBPK model predicted the PK p

SUBMITTER: Chang HP 

PROVIDER: S-EPMC12053227 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature