Comparison of Ussing Chamber and Caco-2 Model in Evaluation of Intestinal Absorption Mechanism of Compounds from Different BCS Classifications.

Abstract

Background: Oral bioavailability (F), which is evaluated by permeability and solubility, is one of the key parameters in drug discovery. Currently, Caco-2 and Ussing chamber are both used in the study of intestinal permeability of drugs at different stages of drug development. However, comparative research between the Ussing chamber and Caco-2 for predicting the intestinal availability data (F_a×F_g) in humans has not been reported.

Methods: In the present study, we evaluated the permeability of 22 drugs in rat intestines by Ussing chamber and compared them with the reported permeability data from Caco-2. In addition, the active transport of gabapentin was evaluated by Ussing Chamber.

Results: Intestine segments were selected by corresponding absorption site for Ussing chamber analysis. BCS Class I and II compounds were more absorbed in the duodenum and jejunum, and Class III and IV compounds were more absorbed in the ileum. P_app values in the Caco-2 model were moderately correlated with human F_a×F_g (R²=0.722), and the P_app of the rat in the Ussing chamber revealed a better correlation with human F_a×F_g (R²=0.952). In addition, we also used the Ussing chamber to identify the transporter of gabapentin, and the results showed that the active absorption of gabapentin was related to LAT1.

Conclusion: Ussing chamber combined with rat intestinal tissue would be a significant tool for predicting the intestinal absorption and metabolism of compounds with diverse physiochemical characteristics.