- Intestinal drug permeability has been recognized as a critical determinant of the fraction dose absorbed, with direct influence on bioavailability, bioequivalence and biowaiver. The purpose of this research was to compare intestinal permeability values obtained by two different intestinal rat perfusion methods: the single-pass intestinal perfusion (SPIP) model and the Doluisio (closed-loop) rat perfusion method. A list of 15 model drugs with different permeability characteristics (low, moderate, and high, as well as passively and actively absorbed) was constructed. We assessed the rat intestinal permeability of these 15 model drugs in both SPIP and the Doluisio methods, and evaluated the correlation between them. We then evaluated the ability of each of these methods to predict the fraction dose absorbed ( F abs ) in humans, and to assign the correct BCS permeability class membership. Excellent correlation was obtained between the two experimental methods ( r 2 = 0.93). An excellent correlation was also shown between literature F abs values and the predictions made by both rat perfusion techniques. Similar BCS permeability class membership was designated by literature data and by both SPIP and Doluisio methods for all compounds. In conclusion, the SPIP model and the Doluisio (closed-loop) rat perfusion method are both equally useful for obtaining intestinal permeability values that can be used for F abs prediction and BCS classification.