Outline of Process for Model Development and Documentation
- Creation of GP a project starts with structure import using ADMET Predictor® Module for both substrates and perpetrators.
–Physicochemical, biopharmaceutical, and biochemical properties
–Initial evaluation via “Chemistry Classification” with all aspects of ADMET
–Extensive literature collection and spreadsheet documentation.
- Workbook with multiple sheets for Compound Properties
- DDI study data for multiple perpetration mechanisms.
–First simulations for “Measured Properties” with parameter sensitivity analysis.
–Model building for individual substrate and/or perpetrator simulations compared to observed data
- Single escalating doses (for nonlinear dose dependence)
- Multiple dosing (for autoinhibition/autoinduction).
–DDI simulations for all appropriate mechanisms on both substrate and perpetrator.
–Analysis of results using the “Guest”* criterion for accuracy of AUC Ratios
Preparation of slides and written reports suitable for regulatory submission.
By Michael Bolger
Presented at SLP MIDD+ Virtual Conference March 3-4, 2021