Quantitative Systems Toxicology Approaches to Understand and Predict Drug-Induced Liver Injury

Authors: Watkins PB
Publication: Clin Liver Dis
Keywords: DILI, DILIsym, modeling, QST, simulation
Software: DILIsym®
Division: PBPK

Key Points

  • The DILI-sim Initiative is a public-private partnership that has applied quantitative systems toxicology modeling to develop software (DILIsym®) that has improved mechanistic understanding of DILI.
  • DILIsym incorporates pharmacokinetics and ability to alter key hepatocyte pathways to predict the frequency and severity of liver injury by drugs in simulated patient populations.
  • Although DILIsym has been largely tested on drugs whose liver safety liability is already established, clinical trials are ongoing that will test its ability to prospectively predict liver safety before clinical trials are conducted.
  • DILIsym also has been useful in optimizing interpretation of traditional liver chemistry tests and is incorporating new and promising biomarkers of liver injury.
  • With further refinement of DILIsym, its predictions of liver safety may reduce the size of clinical trials required to establish liver safety and also may be useful in the clinic in managing DILI risk.

By Paul B Watkins