Application of the ussing chamber technique to assess P-glycoprotein-mediated intestinal drug transport

Abstract

Introduction: Transport proteins play an important role in the intestinal secretion of different drug molecules widely used in veterinary therapeutics. P-glycoprotein (P-gp) secrets a large number of endo-xenobiotic compounds from the intracellular to the extracellular domain by an ATP-dependent process [1]. Different in vitro models have been developed to predict P-gp activity. Caco-2 cell monolayers, derived from a human colonic adenocarcinoma, are widely used to estimate transepithelial passage for different P-gp drug substrates [2]. The use of everted gut sacs has been proposed as a new in vitro model for quantification of the P-gpmediated intestinal drug efflux [3,4]. However, new methodological tools are required to evaluate the physio–pharmacological features of the intestinal drug secretion process in ruminant species. The goal of the current work was to adapt the Ussing chamber technique to the assessment of the P-gp-mediated drug transport in rat and sheep intestine.