Intestinal transport of gentamicin with a novel, glycosteroid drug transport agent.
OBJECTIVE
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.
Axelrod
H R
HR
Intercardia Research Laboratories, Inc., Cranbury, New Jersey 08512, USA. axelrod@irl.intercardia.com
Kim
J S
JS
Longley
C B
CB
Lipka
E
E
Amidon
G L
GL
Kakarla
R
R
Hui
Y W
YW
Weber
S J
SJ
Choe
S
S
Sofia
M J
MJ
D000284:Administration, Oral; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D005839:Gentamicins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006027:Glycosides / Q000493:pharmacokinetics*; D007082:Ileum / Q000378:metabolism; D007408:Intestinal Absorption; D018374:LLC-PK1 Cells; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine; D013656:Taurocholic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014316:Tritium
D005839:Gentamicins; D006027:Glycosides; C118028:TC002; D014316:Tritium; D013656:Taurocholic Acid