Irinotecan PBPK Model for Predicting UGT1A1/CYP3A Drug-Drug Interactions

A supplementary document describes the development and validation of a whole-body physiologically based pharmacokinetic model for the drug irinotecan and its metabolites. The model was calibrated using monotherapy data from 175–300 mg/m² doses and validated across a 33–750 mg/m² dose range, including interactions with ketoconazole, sorafenib, and lopinavir/ritonavir. Bowen Chen authored this document, which was last updated on 2026-05-26.

Use Cases

• Predicting systemic pharmacokinetics of irinotecan and its metabolites based on the described PBPK model structure.
• Assessing UGT1A1/CYP3A-mediated drug-drug interaction risks using the validated inhibitor scenarios.
• Simulating dose-exposure relationships for standard irinotecan regimens as mentioned in the model framework.
• Calibrating pharmacokinetic models using the described monotherapy data from 175–300 mg/m² doses.

Strengths

• Model validation involved 54/56 (96.4%) comparisons meeting a 2-fold acceptance criterion for Cmax and AUC.
• The model was calibrated and validated across a wide dose range from 33 to 750 mg/m².
• Documentation includes specific validation against three inhibitor scenarios: ketoconazole, sorafenib, and lopinavir/ritonavir.

Limitations

• The dataset is a 500.7 KB DOCX file, which is a small supplementary document rather than a primary data repository.
• Row count and column-level documentation are absent; data structure and semantics must be inferred from the text.
• The model overpredicted APC exposure in the ketoconazole scenario, as noted in the results.

Provenance

Source

figshare

Collection Method

Model development and simulation using the Simcyp® platform, as described in the document.

Freshness

Last updated 2026-05-26 06:01:51; freshness should be verified.