A mechanistic, mathematical model (DILIsym�) is under development as a public-private initiative based on the physiological processes involved in drug-induced liver injury.  The model includes scales ranging from molecular/cellular interactions to organ-tissue level considerations.  The primary goals for the model include understanding how in vitro toxicity assay results translate to pre-clinical animal models, the relevance of pre-clinical results for humans, and which emerging biomarkers are most translatable and informative for the clinic.  Simulated mice, rats, and humans accurately reproduce the hepatotoxic responses to acetaminophen, 3'-hydroxyacetanilide (AMAP), methapyrilene, and aflatoxin B-1, providing validation of the DILIsym� model for reactive metabolite mediated toxicity.  Models of events leading to mitochondrial toxicity, bile salt transporter inhibition, and details around the innate immune response are being added in 2012.  Examples of using the DILIsym� model for decision making, experimental design, and increased understanding of DILI will be shared.

Computational prediction of liver toxicity using the DILIsym<sup>TM</sup> model

244th National Meeting (2012)

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Computational prediction of liver toxicity using the DILIsymTM model

Computational prediction of liver toxicity using the DILIsym^TM model