Intestinal transport of gentamicin with a novel, glycosteroid drug transport agent

Purpose. The objective was to investigate the ability of a glycosteroid (TC 002) to increase the oral bioavailability of gentamicin. Methods. Admixtures of gentamicin and TC002 were administered to the rat il eum by injection and to dogs by ileal or jejunal externalized ports, or PO. Bioavailability of gentamicin was determined by HPLC. H-3-TC002 was inject ed via externalized cannulas into rat ileum or jejunum, or PO and its distr ibution and elimination was determined. The metabolism of TC002 in rats was evaluated by solid phase extraction and HPLC analysis of plasma, urine and feces following oral or intestinal administration. Results. The bioavailability of gentamicin was substantially increased in t he presence of TC002 in both rats and dogs. The level of absorption was dep endent on the concentration of TC002 and site of administration. Greatest a bsorption occurred following ileal or jejunal administration. TC002 was sig nificantly more efficacious than sodium taurocholate, but similar in cytoto xicity. TC002 remained primarily in the GI tract following oral or intestin al administration and cleared rapidly from the body. It was only partly met abolized in the GI tract, but was rapidly and completely converted to its m etabolite in plasma and urine. Conclusions. TC002 shows promise as a new drug transport agent for promotin g intestinal absorption of polar molecules such as gentamicin.