While drug-induced liver toxicity has long been a main point of focus of small molecule drug development, understanding the quantitative relationship between hepatotoxicity models, both in vitro and non-human in vivo, remains elusive. To address this weakness in understanding, we have utilized a high-throughput, 3D cell culture platform containing both the cell line HepG2 and primary human hepatocytes. These quantitative relationships suggest a high level of predictivity of in vivo toxicity responses by primary human hepatocytes cultured in three dimensions (~75%), and a moderate predictivity for the hepatoblastoma line HepG2 (~50%). Due to the very low expression levels of drug metabolizing enzymes by HepG2, this disparity in predictivity shows the necessity of including metabolism in considerations made for hepatotoxicity predictions. These results reemphasize the biorelevance of properly designed in vitro systems for prediction of in vivo action, and offer further insight into these relationships than simple qualitative relationships.

In vitro – in vivo toxicity correlations via high-throughput three-dimensional primary hepatocyte culture

2019 Spring National Meeting

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