Removal of residual colonic ciprofloxacin in the rat by activated charcoal entrapped within zinc-pectinate beads

Abstract

Residual antibiotics reaching the colon have many deleterious effects on the colonic microbiota including the selection of new antibiotic resistances. In order to avoid the selection of ciprofloxacin resistance, intestine or colon-targeted zinc-pectinate beads containing activated charcoal (AC) were designed for the inactivation of residual ciprofloxacin in the gastrointestinal tract of rats. Bead stability after oral administration was adjusted by tuning the concentration of zinc in the gelling bath and the number of washings. Intestine and colon-targeted beads were administered along with 50 mg/kg of ciprofloxacin and ciprofloxacin was dosed in the plasma and the feces using HPLC. Ciprofloxacin pharmacokinetics was not affected by the oral co-administration of beads. The co-administration of intestine-targeted beads led to a significant decrease of the residual fecal free ciprofloxacin with a pronounced dose effect. Our study suggests the rat model is not appropriate for the investigation of bacteria responsive colon-targeted beads probably due to the important anatomical and physiological differences between human and rat gastrointestinal tracts. The ability of AC loaded zinc-pectinate beads to selectively decrease the intestinal residual fraction of ciprofloxacin could provide a better protection of the intestinal microbiota and may prevent the emergence of ciprofloxacin resistance in the gastrointestinal tract.