Intestinal Perfusion Methods for Oral Drug Absorptions

The in situ intestinal perfusion model is widely used to predict oral drug absorption and bioavailability. It is an important and popular tool, not only due to its prediction power but also because it elucidates the mechanisms underlying intestinal absorption from the perspectives of transporters and metabolism. This chapter provides an overview of several specific applications in which the in situ perfusion model can be applied to elucidate the absorption, metabolism, and transporter mechanisms. Recent years have seen increased usage of metabolism enzyme or transporter inhibitors and gene knockout animals in perfusion model, which improves the model's accuracy and extends its application. Although the in situ intestinal perfusion model is a good transition model between in vitro and in vivo models, distinct expression levels and patterns for metabolic enzymes and transporters in different species limit the prediction accuracy of drug metabolism and oral bioavailability in humans. An example of a single-pass perfusion study was described, and relevant data analysis was discussed.