Physiologically Based Modeling to Predict Monoclonal Antibody Pharmacokinetics in Humans from in vitro Physiochemical Properties.

ABSTRACT: A model-based framework is presented to predict monoclonal antibody (mAb) pharmacokinetics (PK) in humans based on in vitro measures of antibody physiochemical properties. A physiologically based pharmacokinetic (PBPK) model is used to explore the predictive potential of 14 in vitro assays designed to measure various antibody physiochemical properties, including nonspecific cell-surface interactions, FcRn binding, thermal stability, hydrophobicity, and self-association. Based on the mean plasma PK time course data of 22 mAbs from humans reported in the literature, we found a significant positive correlation (R = 0.64, p = .0013) between the model parameter representing antibody-specific vascular to endothelial clearance and heparin relative retention time, an in vitro

SUBMITTER: Hu S 

PROVIDER: S-EPMC9067474 | biostudies-literature | 2022 Jan-Dec

REPOSITORIES: biostudies-literature