Experimental Data and PBPK Modeling Quantify Antibody Interference in PEGylated Drug Carrier Delivery.

ABSTRACT: Physiologically-based pharmacokinetic (PBPK) modeling is a popular drug development tool that integrates physiology, drug physicochemical properties, preclinical data, and clinical information to predict drug systemic disposition. Since PBPK models seek to capture complex physiology, parameter uncertainty and variability is a prevailing challenge: there are often more compartments (e.g., organs, each with drug flux and retention mechanisms, and associated model parameters) than can be simultaneously measured. To improve the fidelity of PBPK modeling, one approach is to search and optimize within the high-dimensional model parameter space, based on experimental time-series measurements of drug distributions. Here, we employ Latin Hypercube Sampling (LHS) on a PBPK model of PEG-liposomes (PL

SUBMITTER: Talkington AM 

PROVIDER: S-EPMC8576315 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature