Valproic Acid QST Model Integrating PBPK and Hepatic Metabolism

A collection of a quantitative systems toxicology (QST) model integrating a physiologically-based pharmacokinetic (PBPK) model for valproic acid with the HEPATOKIN1 liver metabolism model. It was authored by Vipul Gupta to simulate drug-induced liver injury mechanisms, specifically hepatic triacylglycerol accumulation via CPT1 inhibition. The model includes PPARα-mediated regulatory effects on key liver enzymes.

Use Cases

• Simulate dose-dependent hepatic triacylglycerol (TAG) accumulation resulting from valproic acid's competitive inhibition of CPT1.
• Evaluate the impact of PPARα-mediated regulatory effects on key liver enzymes within the integrated PBPK and HEPATOKIN1 model framework.
• Predict clinically relevant markers of lipid metabolism disruption using the quantitative systems toxicology approach for valproic acid.

Strengths

• Integrates two established computational models: a PBPK model for valproic acid and the large-scale liver metabolism model HEPATOKIN1.
• Model predictions are qualitatively consistent with clinical observations of hepatic steatosis.
• Explicitly includes PPARα-mediated regulatory pathways to ensure biologically consistent outcomes.

Limitations

• Dataset is a 1.7 MB DOCX file, indicating it is likely a document describing the model rather than structured, machine-readable data.
• No columnar data or sample data is available, limiting direct use for standard tabular AI/ML tasks.
• The model is a specific case study on valproic acid, limiting generalizability to other compounds without significant adaptation.

Provenance

Source

figshare

Collection Method

Computational modeling study integrating existing PBPK and HEPATOKIN1 models.

Freshness

Last updated March 20, 2026.