Biotransformation of 20(R/S)-glucopyranosyloxy methylprednisolonates and their evaluation as colonic mucosa-specific pro-antedrugs

Biotransformation of 20 (R/S)-glucopyranosyloxy methylprednisoionates and their evaluation as colonic mucosa-specific pro-antedrugs The fate of 2-0 (R/S) glucopyrauosyloxy methylprednisolonates after the oral administration was examined in rats and guinea-pigs. The glycosides were stable in the small-intestinal contents, but the glycoside bonds were cleaved by the action of bacteria in the large-intestinal contents to release methyl 20(R/S)-dihydroprednisolonates, which were rapidly hydrolyzed to inactive carboxylates in the plasma. The high recovery of the glycosides and the aglycons in the large-intestinal contents after intrajejunal administration of 20(R/S)-glucopyranosyloxy methylprednisolonates in guinea-pigs proved the glycosides to he poorly absorbed from the small intestine. These results suggest that 20 (R/S)-glucopyranosyloxy methylprednisolonates may be orally effective pro-antedrugs, which express the anti-inflammatory activity specifically in the colonic mucosa with no systemic effect.