A quantitative systems pharmacology modeling platform for evaluating triglyceride profiles in patients with high triglycerides receiving evinacumab.

ABSTRACT: A model to quantitatively characterize the effect of evinacumab, an investigational monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3) on lipid trafficking is needed. A quantitative systems pharmacology (QSP) approach was developed to predict the transient responses of different triglyceride (TG)-rich lipoprotein particles in response to evinacumab administration. A previously published hepatic lipid model was modified to address specific queries relevant to the mechanism of evinacumab and its effect on lipid metabolism. Modifications included the addition of intermediate-density lipoprotein and low-density lipoprotein compartments to address the modulation of lipoprotein lipase (LPL) activity by evinacumab, ANGPTL3 biosynthesis and clearance, and a target-mediated drug disp

SUBMITTER: Khaksar Toroghi M 

PROVIDER: S-EPMC8592508 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature