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 a nd gram-positive cocci. As a class, the aminoglycosides are poorly absorbed from the gastrointestinal (GI) tract and are commonly used as injectable a nd topical preparations. This study was aimed at finding the effect of a no vel emulsifier, Labrasol, on the absorption of GM from the GI tract of rats . GM formulations were prepared, either as saline solution or as Labrasol m icroemulsions, and were administrated to rat small intestine and colon. Pla sma GM levels following intestinal application were compared to those obtai ned with intravenous (i.v.) administration. A 5 mg/kg dose of GM preparatio n containing Labrasol, 1 ml/kg, administrated into colon resulted in the me an AUC of 21.179 +/- 1.374 mug x h/ml, compared to 7.813 +/- 0.105 mug x h/ ml obtained with i.v. administration of GM, I mg/kg. The absolute bioavaila bility (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 surf actants (8.4% for Tween 80 and 3.4% for Transcutol P). Additionally, in vit ro permeation studies demonstrated that Labrasol also inhibited the intesti nal secretory transport. The effect of Labrasol is ascribed to both (1) enh anced GM absorption from the GI lumen into the systemic circulation and (2) inhibition of efflux of GM from the enterocytes to the GI lumen. (C) 2001 Elsevier Science Inc. All rights reserved.