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

• Published in: Pharmaceutical research 1998-12, Vol.15 (12), p.1876-1881
• Main Authors: Axelrod, H. R., Kim, J. S., Longley, C. B., Lipka, E., Amidon, G. L., Kakarla, R., Hui, Y. W., Weber, S. J., Choe, S., Sofia, M. J.
• Format: Article
• Language: English
• Subjects: Acids; Administration, Oral; Animals; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bile; Bioavailability; Biological and medical sciences; Cytotoxicity; Drug Delivery Systems - methods; Feces; General pharmacology; Gentamicins - administration & dosage; Gentamicins - blood; Gentamicins - pharmacokinetics; Glycosides - pharmacokinetics; Ileum - metabolism; Intestinal Absorption; Laboratory animals; Life Sciences (General); LLC-PK1 Cells; Male; Medical sciences; Metabolism; Metabolites; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Plasma; Potassium; Rats; Rats, Sprague-Dawley; Small intestine; Space life sciences; Swine; Taurocholic Acid - administration & dosage; Taurocholic Acid - analogs & derivatives; Taurocholic Acid - pharmacokinetics; Tissue Distribution; Tritium; Urine; Veins & arteries
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/A:1011962207882

PURPOSE: The objective was to investigate the ability of a glycosteroid (TC002) to increase the oral bioavailability of gentamicin. METHODS: Admixtures of gentamicin and TC002 were administered to the rat ileum by injection and to dogs by ileal or jejunal externalized ports, or PO. Bioavailability of gentamicin was determined by HPLC. 3H-TC002 was injected via externalized cannulas into rat ileum or jejunum, or PO and its distribution 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 the presence of TC002 in both rats and dogs. The level of absorption was dependent on the concentration of TC002 and site of administration. Greatest absorption occurred following ileal orjejunal administration. TC002 was significantly more efficacious than sodium taurocholate, but similar in cytotoxicity. TC002 remained primarily in the GI tract following oral or intestinal administration and cleared rapidly from the body. It was only partly metabolized in the GI tract, but was rapidly and completely converted to its metabolite in plasma and urine. CONCLUSIONS: TC002 shows promise as a new drug transport agent for promoting intestinal absorption of polar molecules such as gentamicin.