Summary
- Mechanistic (semi-mechanistic) methods are available to predict tissue partitioning (Kp) and Vss from compound properties and tissue physiology.
- Prediction accuracy depends on reliable inputs and method assumptions that match the compound’s distribution mechanisms.
- When predictions miss observed Vss, investigate input uncertainty and missing mechanisms before making empirical adjustments.
- Sensitivity analysis can be used to evaluate which inputs drive Kp and Vss uncertainty for each compound.
By Viera Lukacova
ISSX – 27th North American Meeting, October 11-14, 2026, San Francisco, California