[Antedrugs and pro-antedrugs of corticosteroids]

Corticosteroids for local application, based on the "antedrug" concept, are reviewed. These steroids possess local anti-inflammatory activity, but are rapidly metabolized to inactive compounds upon entry into circulation from the tissue, to which they were applied, resulting in no systemic toxicity. Corticosteroids based on the novel "pro-antedrug" concept are also introduced. These steroids, glycosides of antedrugs, were designed and synthesized for oral treatment of ulcerative colitis. After oral administration, the glycosides are poorly absorbed from the small intestine, so that they can sufficiently reach the colon and be converted to the aglycons by the action of colonic bacteria. The aglycon is the antedrug, which may show local anti-inflammatory activity in the colonic mucosa and be converted to the inactive form upon entry into circulation. Namely, the glycosides of antedrugs may be orally effective "pro-antedrugs", which specifically express the anti-inflammatory activity in the colonic mucosa, with no systemic effect.