Relative anti-inflammatory effect of oral dexamethasone-beta-D-glucoside and dexamethasone in experimental inflammatory bowel disease in guinea-pigs.
The relative anti-inflammatory effect of dexamethasone and a prodrug, dexamethasone-beta-D-glucoside, has been assessed in guinea-pigs with experimentally-induced inflammatory bowel disease (IBD). The glucoside prodrug is designed to reach the large intestine following oral administration. The active agent is liberated when the prodrug is hydrolysed by glycosidases of colonic bacteria. Guinea-pigs were administered degraded carrageenan in their drinking water to produce experimental IBD. Starting on day 15, dexamethasone (1.3 mumol kg-1) or dexamethasone-beta-D-glucoside (1.3 or 0.65 mumol kg-1) was administered by gastric intubation once daily for 5 days. Relative to control animals, the drug and prodrug treatments significantly (P less than 0.05) reduced the total number of caecal ulcers. While there was no difference statistically between the drug and prodrug treatments, the data suggest that a lower dose of dexamethasone, administered as its glucoside prodrug, could reduce side-effects without reduced efficacy. These results support the hypothesis that localized delivery of dexamethasone to the large bowel can improve pharmacotherapy of IBD by reducing the side-effects associated with corticosteroids.
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Biopharmaceutics Research Group, SRI International, Menlo Park, CA 94025.
Phillips
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McLeod
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Tozer
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D000818:Animals; D000893:Anti-Inflammatory Agents; D001835:Body Weight / Q000187:drug effects; D002351:Carrageenan; D003907:Dexamethasone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004326:Drinking / Q000187:drug effects; D006168:Guinea Pigs; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone; C040551:dexamethasone 21-glucoside; D002351:Carrageenan