A human population-based organotypic in vitro model for cardiotoxicity screening_suppl

Abstract

progress has been achieved in incorporating population pharmacokinetics to address variability in the processes of absorption, distribution, metabolism, and excretion, including use of in silico and in vitro methods (Jamei, 2016). Indeed, population-based in vitro-in vivo extrapolation (IVIVE) to address pharmacokinetic variability is an increasingly common step in safety evaluations for both pharmaceuticals and environmental chemicals (Bell et al., 2017;Wetmore, 2015). However, it is well-recognized that pharmacodynamic processes likely contribute equally, if not more, to inter-individual variability (Turner et al., 2015;Zeise et al., 2013;Hattis and Lynch, 2007). Existing examples of in vitro studies aimed at characterizing pharmacodynamic components of population variability for drugs or environmental chemicals have been conducted either in human lymphoblast cell lines (Abdo et al., 2015) or induced pluripotent stem cells (iPSC) derived from individuals with familial syndromes (Li et al., 2017). The