Model-based contextualization of in vitro toxicity data quantitatively predicts in vivo drug response in patients.

ABSTRACT: Understanding central mechanisms underlying drug-induced toxicity plays a crucial role in drug development and drug safety. However, a translation of cellular in vitro findings to an actual in vivo context remains challenging. Here, physiologically based pharmacokinetic (PBPK) modeling was used for in vivo contextualization of in vitro toxicity data (PICD) to quantitatively predict in vivo drug response over time by integrating multiple levels of biological organization. Explicitly, in vitro toxicity data at the cellular level were integrated into whole-body PBPK models at the organism level by coupling in vitro drug exposure with in vivo drug concentration-time profiles simulated in the extracellular environment within the organ. PICD was exemplarily applied on the hepatotoxicant azathiop

SUBMITTER: Thiel C 

PROVIDER: S-EPMC5306109 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature