The situation
The animal model works and GLP toxicology is done. Now the starting dose has to be defended in an IND or CTA.
What we do
- Predict human PK by allometry and by PBPK, then reconcile
- Find the driver of effect: peak, AUC, or time above threshold
- Translate on exposure, not dose
What you get
- Predicted human profile, assumptions stated
- Starting dose and escalation, with the rationale
- A Phase I sampling schedule that informs the model
Regulatory basis
The starting dose is among the first things a reviewer scrutinises. A rationale tied to the toxicology exposures is far easier to defend than an unexplained scaling factor.