Physiologically Based in Silico Models for the Prediction of Oral Drug Absorption

The ability to accurately predict the oral absorption of drugs based solely on in vitro data provides an opportunity to assess the developability, from an absorption point of view, of new chemical entities before any preclinical or clinical in vivo studies are performed. There have been several reports on physiologically based mathematical models that are capable of producing such predictions, and there are a few commercially available software packages (e.g., GastroPlus™, iDEA™, Intellipharm®PK, and PK-Sim®) that have been shown to predict the human absorption properties with a fairly high degree of accuracy. As these models use the interplay between the drug characteristics and the human physiology to simulate the processes involved in the oral absorption of drugs, they also give information about the underlying mechanisms for absorption limitations and as such they are well suited to be used in progressing new chemistry and to support formulation development. The aim of this chapter is to briefly summarize the underlying principles for some of the physiologically based in silico models for the prediction of human absorption and to discuss their relative performance as well as limitations in their use.