In-vitro to in-vivo acetaminophen hepatotoxicity extrapolation using classical schemes, pharmaco-dynamic models and a multiscale spatial-temporal liver twin
In vitro to in vivo extrapolation represents a critical challenge in toxicology. In this paper we explore extrapolation strategies for acetaminophen (APAP) based on mechanistic models, comparing classical homogeneous compartment pharmaco-dynamic (PD) models and a multiscale digital twin model resolving liver microarchitecture at cellular resolution. The models integrate consensus detoxification reactions in each individual hepatocyte. We study the consequences of the two model types on the extrapolation and show in which cases these models perform better than the classical extrapolation strategy that is based either on the maximal drug concentration (Cmax) or the area under the pharmaco-kinetic curve (AUC) of the drug blood concentration.
@article{arxiv.2210.08796,
title = {In-vitro to in-vivo acetaminophen hepatotoxicity extrapolation using classical schemes, pharmaco-dynamic models and a multiscale spatial-temporal liver twin},
author = {Jules Dichamp and Geraldine Cellière and Ahmed Ghallab and Reham Hassan and Noemie Boissier and Ute Hofmann and Joerg Reinders and Selahaddin Sezgin and Sebastian Zühlke and Jan Hengstler and Dirk Drasdo},
journal= {arXiv preprint arXiv:2210.08796},
year = {2023}
}