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Apr 20, 2021
  |  Presentation

Assessing the Potential for Hepatotoxicity for Combination Therapy of Valproate (VPA) and CBDusing Quantitative Systems Toxicology (QST) DILIsym Correctly Predicts CBD ALT Elevations and Evaluates Interaction Mechanism(s)

Project Scenario and Goal

  • Epidiolex (highly purified CBD) is efficacious in treating seizures associated with Dravetsyndrome (DS), Lennox-Gastautsyndrome (LGS), and Tuberous Sclerosis Complex (TSC)
  • In the clinical trials of these patients, ALT elevations were seen in 21% of trial participants taking CBD with concomitant valproate (VPA) compared with 3% in participants not taking VPA [Epidiolexprescription info]
  • GOAL: To identify the mechanism(s) accounting for the higher incidence of ALT elevation observed during concomitant treatment with VPA and CBD by using a Quantitative Systems Toxicology (QST) model of hepatotoxicity (DILIsym®)
  • HYPOTHESIS: Increased incidence of ALT elevations was due to VPA and CBD (or metabolites of each) inhibiting mitochondrial respiration

By Vinal Lakhani

Presented at AASLD FDA DILI Conference April 20-21, 2021

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