PK / PD Modeling Overview
- Conducted using either a compartmental PK model or a PBPK model
- Applies to both small and large molecules
- Often combined with scaling to develop a predictive PK/PD human model
Common Uses
- Dose regimen design
- Interspecies scaling / Phase I exposure predictions
- Assessment of potential impacts on efficacy from PK changes (due to material lot changes)
- Preclinical & clinical optimization study design
Regulatory Guidance & Timing
PK/PD modeling is not specifically required in regulatory guidance, but the FDA has strongly suggested including modeling in the data package. In addition, the 2017 EMA guideline for first-in-human (FIH) dosing recommends that estimation of FIH should be based on state-of-the-art modeling (e.g. PK/PD and PBPK) and or using allometric factors. A PK/PD model can be critical for predicting FIH doses of large molecules with approaches using a minimally anticipated biological effect level (MABEL) or a pharmacologically active dose (PAD).
PK / PD modeling studies typically occur during late discovery through clinical.
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