Simulations Plus

Discuss advances made with PBPK modeling for both oral and non-oral routes for the first in human predictions

Providing a case for why you should focus on preclinical verification when using Physiologically Based Pharmacokinetic (PBPK) modeling for First-In-Human (F.I.H) pharmacokinetic predictions.

Drug-induced kidney injury or acute kidney injury (AKI) is one of the major reasons for drug failure behind cardiovascular and liver injuries

QSP models are designed to characterize biological systems, representing details such as disease pathophysiology, drug pharmacology, and pathways of toxicity

What are we doing for inhaled products today?

Epidiolex (highly purified CBD) is efficacious in treating seizures associated with Dravetsyndrome (DS), Lennox-Gastautsyndrome (LGS), and Tuberous Sclerosis Complex (TSC)

Some patients treated with Drug X experienced elevations in serum bilirubin with concomitant ALT elevations, potentially indicative of severe liver injury.

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.

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.

Slides from the OPCO Fireside Chat

GastroPlus applications to various drug delivery routes of administration.

An introduction to Model-Informed Drug Development (MIDD) for Malaria and Volunteer Infection Studies (VIS)

This talk will present how quantitative systems toxicology (QST) modeling can aid in evaluating potential drug-drug interactions.