Minimal brain PBPK model to support the preclinical and clinical development of antibody therapeutics for CNS diseases.

ABSTRACT: There are several antibody therapeutics in preclinical and clinical development, industry-wide, for the treatment of central nervous system (CNS) disorders. Due to the limited permeability of antibodies across brain barriers, the quantitative understanding of antibody exposure in the CNS is important for the design of antibody drug characteristics and determining appropriate dosing regimens. We have developed a minimal physiologically-based pharmacokinetic (mPBPK) model of the brain for antibody therapeutics, which was reduced from an existing multi-species platform brain PBPK model. All non-brain compartments were combined into a single tissue compartment and cerebral spinal fluid (CSF) compartments were combined into a single CSF compartment. The mPBPK model contains 16 differential equa

SUBMITTER: Bloomingdale P 

PROVIDER: S-EPMC8604880 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature