Barriers to Oral Bioavailability – An Overview

Oral administration is the preferred route for most medications and is often a prerequisite for development of drugs that are used chronically. Oral bioavailability is essential to avoid so-called “oral bioavailability penalty,” in that drug candidates with low and highly variable oral bioavailability are almost certain to be ruled out for further development as the cost (in both time and resources) of running their trial becomes prohibitive. Good oral bioavailability (ideally >70%) can be achieved by design if factors impacting oral bioavailability are considered during the drug design process. Importantly, in the decades since the development of renin and HIV inhibitors in the early 1990s, poor exposure due to bioavailability insufficiency has drastically reduced from 29% to 13%. Therefore, it is important to educate the scientists involved in the drug design and discovery process the importance of considering factors that associate with oral bioavailability so that future oral drugs will be safer, more effective, and less likely to be involved in drug–drug interactions. Chapter Unavailable provides an overview of the factors that will lead to good oral bioavailability and challenges we face to improve oral bioavailability. Chapter Unavailable also serves to lead the readers to understand the link between various factors and proposed solution presented in this book.