PBSS Workshop – Understanding and Overcoming High Clearance and Poor Bioavailability: Fundamentals, Investigations and Strategies for Drug Discovery

Poor exposure following oral administration is a common challenge facing discovery programs and consequently a frequent focus for DMPK scientists. Frequently, potent compounds cannot be further developed due to less-than-ideal ADME (absorption, distribution, metabolism, and excretion) properties that prevent the compounds to be available following oral administration. Beyond the discovery phase the importance of understanding and optimizing oral exposure continues in the preclinical and ultimately clinical phases of drug development. Inadequate oral exposure could be due to suboptimal physicochemical properties, or problems in absorption from the gut, or first-pass metabolism in the gut and liver, or high intrinsic clearance of the compounds.

The focus of this workshop/symposium is on: 1) to identify and learn about the issues that contribute to low oral exposure, 2) to discuss approaches that one could use to overcome those challenges, 3) to present additional methodologies that can aid in solving exposure problems and 4) to provide suggestions on how to work with partners in Medicinal Chemistry and Biological Sciences within Project Teams.

This workshop/symposium will cover the following topics:

• Pharmacokinetic concepts – absorption, bioavailability, and clearance factors contributing to low oral exposure
• Physiological factors that affect oral exposure
• Physicochemical factors that influence oral exposure
• Metabolism-based issues that give rise to poor oral exposure
• Transporter-based issues that give rise to poor oral exposure
• How to identify the source of problem in oral exposure – properties of the molecules or conditions of the experiment?
• Biopharmaceutical Aspects of oral drug exposure
• Approaches to overcome oral exposure issues, including case studies
• Enabling Exposure of ADME Challenged compounds
• What do Medicinal Chemists/Biologists want and how can we work with them

Find out more on the Pharmaceutical and Bioscience Society website.