By Sachin Lohani
Oral bioavailability, the fraction of an orally administered drug that reaches systemic circulation, is arguably the most important property in drug design and development. In contrast with the intravenous administration where the drug is directly and fully available in the bloodstream, orally administered drugs must be first absorbed in the gastro intestinal tract and then escape first-pass extraction to reach the systemic circulation and ultimately the site of action.
Drug candidates with low oral bioavailability often fail prior to reaching the market due to difficulty in achieving adequate oral exposure for toxicity evaluation. Therefore, the ability to achieve the requisite systemic exposures is critical to the success of preclinical safety studies, as well as to the viability of new drug candidates in the clinic. When an exposure issue is encountered, it is essential to understand the contribution of physicochemical and pharmacokinetic properties to the problem so that the correct strategy can be adopted to enhance exposure.
Oral absorption is also a rapidly evolving scientific field starting with the development of the pH partition hypothesis in the 1950s, defining bioavailability in the 1970s, the emergence of the biopharmaceutical classification system (BCS) in the 1990s, and biopharmaceutical drug disposition classification system (BDDCS) in the mid 2000s. Now, more than ever, scientists need to stay abreast of the latest information in order to understand the root cause of low bioavailability early in drug discovery.
The Good Oral Candidates 101 ecourse provides a step-by-step guide through the fundamentals of achieving optimal oral exposure. After participating in this course, the participants will have a high level understanding of:
- Oral absorption and the impact of phase and formulation design;
- GI physiology;
- Drug metabolism and transporters;
- In vitro and in vivo screening tools;
- PBPK-based approaches to model oral absorption.
This comprehensive, 11-lecture course provides insights from the experts on the fundamental causes behind oral exposure issues and the tools that can be used to investigate them all from the comfort of your home or office.
My fellow members of the CORE team are acknowledged below for their hard work in constructing this diverse, innovative, and broadly applicable eCourse: Nicole Buist, Ph.D.; Anand Balakrishnan, Ph.D.; Annette Bak, Ph.D.; James Polli, Ph.D.; Nathaniel Catron, Ph.D.; Dennis Leung, Ph.D.; Akash Jain, Ph.D.; and Nikoletta Fotaki, Ph.D.
Disclaimer: The views expressed in this work do not necessarily represent the views of the FDA or the United States.