Regarding in vitro systems, JP2 solubility , PAMPA , and Caco-2 are well-known methods for predicting drug absorption in humans at the non-clinical stage. However, the mechanism of absorption is too complex and is related to the diffusion of the compound for solubility , membrane permeability , and active efflux transport by transporters, such as P-gp . Therefore, it is difficult to predict the human Fa with high accuracy, even if any of these in vitro experiments are combined. In ex vivo experiments, in situ perfusion through isolated intestinal segments in rats is well known; however, it is not a perfect predictor of absorption . In in vivo experiments, specifically animal PK experiments, only research on soluble compounds have been performed, and the Fa values of rats and monkeys could be extrapolated to humans . However, there is a lack of sufficient data regarding solubility and dissolution .