Effect of age on gastrointestinal absorption of tobramycin in rats

Abstract

Using newborn, suckling, weanling and adult rats, we studied the effect of age on the intestinal absorption of tobramycin, which is poorly absorbed in adult humans. The mean (±S.D.) bioavailability ( F) values after administering tobramycin (30 mg/kg) orally to newborn, suckling and weanling rats were 39.4 ± 5.8, 19.9 ± 4.6, and 2.8 ± 0.9%, respectively (significant differences). A marked difference was observed between suckling and weanling rats. After duodenal administration of tobramycin (30 mg/kg) to suckling rats, absorption occurred more readily than in adult rats ( F = 104.0 ± 33.6 vs 27.2 ± 5.7%), and the mean F values for both ages were significantly higher than those in the respective oral sham experiments. Therefore, a high concentration of tobramycin in the intestine promotes intestinal absorption. When the cumulative amounts of tobramycin transferred from the mucosal to serosal side were determined in suckling, weanling and adult rats by an everted sac method, the amount was highest for suckling rats, with an abrupt change being found between suckling and weanling rats. The permeation of tobramycin from the mucosal to serosal side was not a saturable process in rats of all ages. An aminoglycoside (AMG), neomycin (10 mM), and a polyamine, spermine (10 mM), significantly increased the permeating of tobramycin in the jejunum and ileum of suckling rats and the jejunum of adult rats. Choline chloride (10 mM), tetraethylammonium (10 mM) and 2,4-dinitrophenol (0.5 mM) did not affect the permeation of tobramycin in any small intestinal regions (jejunum and ileum) of either suckling or adult rats. The following conclusions were drawn: (1) tobramycin absorption occurs readily from the small intestine of suckling rats, but markedly decreases during the weaning period; (2) tobramycin is transferred predominantly via passive diffusion in the immature small intestine of suckling rats; and (3) the intestinal absorption of tobramycin can be enhanced by direct delivery of a high drug concentration exposed to the small intestine, and this absorption is further facilitated with other AMGs or polyamines in the small intestine, particularly in suckling rats.