Challenges in the prediction and modeling of oral absorption and bioavailability.

To predict the performance of a drug following oral dosing, a thorough understanding of the dissolution, uptake and metabolism of the compound is required. In this review, approaches to in silico modeling of these processes are discussed. Although oral absorption, which is limited by dissolution and passive permeation, is to some extent predictable, bioavailability, which is influenced by first-pass metabolism in the intestines and liver, is much more difficult to predict. Much of the difficulty in predicting oral absorption and bioavailability is in the experimental quantification of solubility in the gastrointestinal tract lumen, membrane permeability, plasma protein binding, metabolism and active transport, rather than the formulating of the mathematical models.