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 sol-ubility, is one of the key parameters in drug discovery. Currently, Caco-2 and Ussing cham-ber 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 (Fa×Fg) 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 cham-ber analysis. BCS Class I and II compounds were more absorbed in the duodenum and jeju-num, and Class III and IV compounds were more absorbed in the ileum. Papp values in the Caco-2 model were moderately correlated with human Fa×Fg (R2=0.722), and the Papp of the rat in the Ussing chamber revealed a better correlation with human Fa×Fg (R2=0.952). In addi-tion, we also used the Ussing chamber to identify the transporter of gabapentin, and the re-sults 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 physio-chemical characteristics.