A novel emulsifier, labrasol, enhances gastrointestinal absorption of gentamicin.
Gentamicin (GM) is an important aminoglycoside antibiotic for the treatment of infections caused by a wide spectrum of aerobic gram-negative bacilli and gram-positive cocci. As a class, the aminoglycosides are poorly absorbed from the gastrointestinal (GI) tract and are commonly used as injectable and topical preparations. This study was aimed at finding the effect of a novel emulsifier, Labrasol, on the absorption of GM from the GI tract of rats. GM formulations were prepared, either as saline solution or as Labrasol microemulsions, and were administrated to rat small intestine and colon. Plasma GM levels following intestinal application were compared to those obtained with intravenous (i.v.) administration. A 5 mg/kg dose of GM preparation containing Labrasol, 1 ml/kg, administrated into colon resulted in the mean AUC of 21.179+/-1.374 microg x h/ml, compared to 7.813+/-0.105 microg x h /ml obtained with i.v. administration of GM, 1 mg/kg. The absolute bioavailability (BA) of the Labrasol preparation was 54.2%. Labrasol facilitates the transmucosal delivery of GM from rat colon by forming microemulsions, and the BA obtained with Labrasol microemulsion was higher than with other surfactants (8.4% for Tween 80 and 3.4% for Transcutol P). Additionally, in vitro permeation studies demonstrated that Labrasol also inhibited the intestinal secretory transport. The effect of Labrasol is ascribed to both (1) enhanced GM absorption from the GI lumen into the systemic circulation and (2) inhibition of efflux of GM from the enterocytes to the GI lumen.
Hu
Z
Z
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Japan. takada@mb.kyoto-phu.ac.jp
Tawa
R
R
Konishi
T
T
Shibata
N
N
Takada
K
K
D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D004655:Emulsions / Q000494:pharmacology; D005079:Excipients / Q000494:pharmacology*; D005839:Gentamicins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005989:Glycerides; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009930:Organic Chemicals; D051381:Rats; D017208:Rats, Wistar
D000900:Anti-Bacterial Agents; D004655:Emulsions; D005079:Excipients; D005839:Gentamicins; D005989:Glycerides; D009930:Organic Chemicals; C440220:Labrasol