Effect of triglyceride on small intestinal absorption of cefoxitin in rats

Coadministration of trilaurin or monolaurin with sodium cefoxitin increased its absorption from the small intestine of the rat. Its absorption from the rectum was effected to a lesser extent except when lipase was present. Lipase, a natural constituent of the small intestine fluid, may therefore be essential for the adjuvant action of trilaurin on cefoxitin absorption across the intestinal membrane. Among the triglycerides used, trilaurin and tricaprin were the most effective enhancers of cefoxitin absorption. Both the rate of degradation of triglyceride to its fatty acid component and subsequently the rate of fatty acid absorption were factors influencing the enhancing action. Maintenance of fatty acid concentration at the small intestinal absorption site was shown to be necessary to obtain a cefoxitin bioavailability of up to 70%.     

Changes in Intestinal Mucosal Permeability Caused by Nonprotein Thiol Loss in Rats

The barrier selectivity of the intestinal mucosal membrane permeability may be impaired in certain disease conditions. Membrane permeability was previously shown to be correlated with changes in nonprotein thiol in rat intestinal tissue by the everted sac method. In the present study, the mucosal effects of alloxan-induced diabetes and chronic alcohol administration to intact rats, as well as pre-treatment with diethyl maleate, ethanol, and salicylate, were investigated. In each case, a drop of mucosal nonprotein thiol was associated with an increased absorption of cefoxitin, cefmetazole, and phenol red, hydrophilic compounds that are poorly absorbed through intact membrane, and with a decreased absorption of L-phenylalanine. The effect of nonprotein thiol loss on rectal absorption of cefoxitin, cefmetazole, and phenol red was greater than that on the small intestinal absorption. The increase in phenol red absorption by diethyl maleate in the in vitro everted sac method correlated with Ca²⁺ release from the intestinal mucosa, which was induced by nonprotein thiol loss. Resistance to the effect of nonprotein thiol loss on Ca²⁺ homeostasis was greater in rat ileum than in rat colon (including rectum). The administration of cysteamine as an exogenous nonprotein thiol restored non-protein thiol levels in the mucosa along with the barrier function of the intestinal mucosa to the absorption of cefoxitin, cefmetazole, and phenol red. In contrast, the transport of L-phenylalanine in the small intestinal mucosa was not restored by cysteamine treatment.     

Lymphatic transport of sodium cefoxitin in the presence of sodium 5-methoxysalicylate after injection into rat rectal connective tissue, femoral muscle and femoral vein

Lymphatic uptake of sodium cefoxitin after injection into rectal connective tissue was greater than after injection into the femoral muscle of rats. Coadministration with sodium 5-methoxysalicylate enhanced lymphatic drug uptake at both sites. This enhancement may be an indirect result of 5-methoxysalicylate's suppression of vascular permeation of the cefoxitin. An adjuvant-induced increase in lymphatic fluid flow may also be partially involved in the enhancement of cefoxitin lymphatic transport.