Ciprofloxacin permeability and its active secretion through rat small intestine in vitro

The biopharmaceutical aspect of the fluoroquinolones-metal cations interaction, which reduces antibacterial agents bioavailability and the mechanism of the fluoroquinolone intestinal efflux are still poorly understood. The purpose of this work was to gain further insights into these two issues by measuring the permeability of ciprofloxacin through the rat small intestine in side-by-side diffusion chambers using different incubation media and transport inhibitors. The permeability of ciprofloxacin from the mucosal to the serosal side was low. It was not influenced by the different concentrations of Ca(2+) and Mg(2+) in the donor solution. The active efflux of ciprofloxacin was the highest in the region of the rat small intestine excised proximal to the ileo-caecal junction or when the pH value of the incubation saline was slightly acidic. Thus ciprofloxacin appears to be transported in its cationic or in its zwitterionic form. The efflux was not inhibited by verapamil, benzbromarone or quinidine, which were added to the mucosal side of the intestinal tissue. It was however inhibited by quinidine added to the serosal side. The active secretion is therefore most probably a consequence of the organic cation transporter 1 activity at the basolateral membrane of enterocytes.