COLON-SPECIFIC DRUG DELIVERY FROM A GLUCOSIDE PRODRUG IN THE GUINEA-PIG - EFFICACY STUDY

The effect of a prodrug-based colonic delivery system on carrageenan-induced inflammatory bowel disease (IBD) in guinea-pigs was investigated. Guinea-pigs were administered 4 wt.% of degraded carrageenan in the drinking water for 2 weeks to induce experimental IBD. The prodrug, dexamethasone-beta-D-glucoside, was then administered at one of two dose levels (1.3 or 0.65-mu-mol/kg) once daily by gastric intubation for 5 days; dexamethasone (1.3-mu-mol/kg) was also administered in the same manner. The higher dose of dexamethasone-beta-D-glucoside led to reduced gross pathologic effects (fluid cecal contents, redness, edema, ulcerations), and a significantly lower histopathologic score relative to dexamethasone, which was ineffective at controlling the inflammatory response relative to control animals. The lower dose of prodrug was somewhat more effective than dexamethasone or no drug treatment in controlling gross pathologic effects of the large intestine, but was ineffective when evaluated histologically. The implications of these findings are discussed.