Making a Splash in the US Market: How PBPK Modeling is Playing a Central Role in Risk Reduction

Rapid and efficient development of drug candidates is increasingly important for pharmaceutical companies with accelerated timelines and funding constraints. However, many early drug candidates have poor oral absorption properties making it challenging to achieve target pharmacokinetic (PK) profiles. Without upfront knowledge of absorption risks and mitigation strategies, poor absorption can significantly impact preclinical and clinical study timelines and costs.

Physiologically-based pharmacokinetic (PBPK) modeling software, such as the GastroPlus® platform from Simulations Plus, simulates dynamic physiological factors impacting oral performance. When coupled with in vitro measurements, PBPK modeling is effective in early development for 1) identifying absorption risks, 2) assessing the potential for solubility enhancing formulations such as salts, cocrystals, or amorphous solid dispersions to mitigate these risks, and 3) designing and optimizing preclinical and clinical studies with respect to dose, prandial state, or gastric pH modification to maximize the likelihood of achieving desired PK profiles.

In this presentation, we will demonstrate how PBPK models combined with Lonza’s custom and off-the shelf in vitro tools and solubility enhancement expertise can be used to identify and mitigate absorption risks in early drug development, reducing the need for drug product reformulation or repeated preclinical or clinical studies.

Key Learning Objectives:

• Learn how PBPK modeling can identify potential oral absorption risks and mitigation strategies (e.g. bioavailability enhancement) for early drug candidates.
• Learn how PBPK modeling coupled with in vitro testing can guide early selection of drug form and formulation to achieve clinical study goals.
• Gain insights into how key drug and formulation factors including solubility, permeability, and dissolution rate can impact absorption risks such as poor oral bioavailability, food-drug interactions, and pH-dependent DDI effects.