Assessment of intestinal drug transport: development and application of the using chamber technique

Abstract

The role of the transport protein P-glycoprotein (P-gp) in the pharmacokinetics of different drugs used in veterinary medicine has been demonstrated. The goal of the current work was to develop the Ussing chamber technique to characterize the intestinal P-gp-mediated drug transport in rats and sheep. The flat sheets of intestinal mucosa (ileum) were mounted into Ussing chambers. Digoxin (DGX) (200 µM) and Albendazole sulfóxido (ABZSO) (30 µM) were added to mucosal (M) and serosal (S) sides. Samples were taken between 30 and 240 min. DGX and ABZSO were analyzed by HPLC. The efflux rate (Peff) was calculated. The intestinal transport of DGX and ABZSO was corroborated. In rats, the Peff S-M was significantly higher than Peff M-S for both compounds. The PeffS-M/PeffM-S ratio ranged between 1.76 and 2.37 for both drugs, indicating a transport process to the intestinal lumen. In sheep, the PeffS-M/PeffM-S ratio for ABZSO was 1.49. The presence of PSC833 enhanced the efflux M-S in both species. The PeffS-M/PeffM-S ratio decreased to 1.23 (rats) and 1.30 (sheep). The use of the Ussing chamber technique is a useful tool to improve the comprehension of the absorption/excretion mechanisms involved in the transport of drugs therapeutically used in veterinary medicine.