Physiologically Based Pharmacokinetic (PBPK) and Receptor Occupancy (RO) modeling are quantitative, mechanistic approaches used to describe how a drug is absorbed, distributed, metabolized, and eliminated in the body, and how it interacts with its biological target. PBPK/RO modeling provides a mechanistic link between dose and pharmacological effect.
PBPK/RO modeling helps guide dose selection (particularly first-in-human dose), de-risk development, and support confident clinical and regulatory strategy by providing a mechanistic, physiology-driven insight into drug disposition and target interaction.
Key Questions PBPK/RO Modeling Can Answer
- What dose is expected to achieve sufficient target occupancy?
- How does drug exposure differ between tissues, organs, or patient populations?
- How can animal or in vitro data be translated to humans?
- What dosing regimens maximize target engagement while minimizing risk?
- How do physiological changes or drug-drug interactions affect exposure and efficacy?
Case Studies
QSP Model to Predict Target Occupancy by BTK Inhibitors in Patients With B-Cell Malignancies
Pharmacokinetics modeling and optimal dose prediction for a bispecific antibody against CD40 and PD1
