Quantitative systems toxicology (QST) to investigate mechanisms contributing to clinical bilirubin elevations

Quantitative systems toxicology (QST) to investigate mechanisms contributing to clinical bilirubin elevations

Conference: AASLD
Software: DILIsym®
Division: DILIsym Services

To be presented at the FDA/CDER and AASLD 2021 DILI Conference XVIII. Quantitative systems toxicology (QST) to investigate mechanisms contributing to clinical bilirubin elevations: Some patients treated with Drug X experienced clinically relevant elevations in serum bilirubin with concomitant ALT elevations, indicative of potentially severe liver injury (Hy’s Law cases). However, the interpretation is complicated if there is evidence that a compound directly alters bilirubin disposition, leading to bilirubin elevations absent liver injury. Distinguishing between these two possibilities is critical to inform drug development decisions. DILIsym, a QST platform of drug-induced liver injury (DILI), was used to investigate the interpretation of putative Drug X-related elevations in liver biomarkers.

Assessing the Potential for Hepatotoxicity for Combination Therapy of Valproate (VPA) and (CBD) using Quantitative Systems Toxicology (QST)

Assessing the Potential for Hepatotoxicity for Combination Therapy of Valproate (VPA) and (CBD) using Quantitative Systems Toxicology (QST)

Conference: AASLD
Software: DILIsym®
Division: DILIsym Services

To be presented at the FDA/CDER and AASLD 2021 DILI Conference XVIII. Assessing the Potential for Hepatotoxicity for Combination Therapy of Valproate (VPA) and (CBD) using Quantitative Systems Toxicology (QST). We aimed to identify the mechanism(s) accounting for the higher incidence of ALT elevation observed in individuals treated with VPA and CBD by using a Quantitative Systems Toxicology (QST) model of hepatotoxicity (DILIsym®) to test the hypothesis that increased incidence of ALT elevation was due to VPA and CBD (or metabolites of each) inhibiting mitochondrial respiration.

Utilization of PBBM/PBPK Models for Building a Safe Space and Regulatory Applications in Support of Drug Product Quality

Utilization of PBBM/PBPK Models for Building a Safe Space and Regulatory Applications in Support of Drug Product Quality

Authors: Suarez-Sharp S
Software: GastroPlus®
Division: Simulations Plus

Drug products undergo many chemistry, manufacturing, and control (CMC) changes throughout their lifecycle, making the overall process costly and time consuming.

DILIsym Simulations Support the Liver Safety of Ubrogepant in New Toxicological Sciences Publication

DILIsym Simulations Support the Liver Safety of Ubrogepant in New Toxicological Sciences Publication

Software: DILIsym®
Division: DILIsym Services

Dr. Paul B. Watkins and Dr. Jeff Woodhead discuss the DILIsym analysis of the latest publication in Toxicological Sciences! Small-molecule calcitonin gene...