hoe-777 and hydrocortisone-17-butyrate-21-propionate

Nonhalogenated double esters of prednisolone or hydrocortisone applied topically to the skin have a low atrophogenic potential. However, activity and benefit/risk ratio and therefore the superiority over conventional topical glucocorticoids are not well defined.. The activities of cream preparations with prednicarbate (0.025% to 0.25%), hydrocortisone aceponate, and hydrocortisone buteprate (0.1%) are compared to the effects of betamethasone 17-valerate (0.1%), hydrocortisone (1%), and two drug-free vehicles in 60 healthy volunteers. Test models are the skin blanching assay (occluded and nonoccluded mode), ultraviolet-induced erythema, and an irritant (sodium dodecyl sulfate) dermatitis. The benefit/risk ratio is derived from the activity in the former models and the reduction of skin thickness as determined previously.. Prednicarbate activity increases in a dose-dependent manner. Prednicarbate, 0.25%, and the hydrocortisone double esters appear to be equipotent to betamethasone 17-valerate in the skin blanching test and the ultraviolet-erythema test, but superior to hydrocortisone and the vehicles. Prednicarbate and its vehicle, however, do not reverse irritant dermatitis. The benefit/risk ratios of prednicarbate and hydrocortisone aceponate exceed those with betamethasone 17-valerate.. Prednicarbate and hydrocortisone aceponate are intermediate potent glucocorticoids that are superior to betamethasone 17-valerate because of the improved benefit/risk ratio. Patients with severe atopic dermatitis and those who relapse frequently should profit from the treatment with these newer glucocorticoids.

Topics: Administration, Topical; Adult; Anti-Inflammatory Agents; Betamethasone Valerate; Dose-Response Relationship, Drug; Double-Blind Method; Drug Eruptions; Female; Humans; Hydrocortisone; Male; Prednisolone; Reference Values; Skin

Topics: Administration, Cutaneous; Adult; Betamethasone Valerate; Double-Blind Method; Drug Evaluation; Erythema; Female; Humans; Hydrocortisone; Male; Prednisolone; Skin; Ultraviolet Rays; Vasoconstriction

Recently several attempts have been made to develop glucocorticoids which show less pronounced side effects. We intended, therefore, to use experimental systems to examine the influence of newly developed nonhalogenated glucocorticoids and conventional fluorinated congeners, demonstrating similar anti-inflammatory activity in vivo, on biosynthetic capacities of human fibroblasts. Fibroblasts were kept in monolayer cultures and exposed to different concentrations of the active compounds for 6 days to analyze the influence on proliferation. Chemotaxis of fibroblasts was studied in blind well Boyden chambers. Fibroblast-conditioned medium was used as chemoattractant. All glucocorticoids tested influenced fibroblast proliferation at high (10(-5) M) and low (10(-9) M) concentration. Yet the effect was clearly more marked with fluorinated compounds. Basically, the same applied for chemotaxis. At the low concentration, however, nonfluorinated glucocorticoids exerted almost no influence. These results suggest that modifications of steroidal structure can specifically influence their effects on biosynthetic capacities of fibroblasts.

Topics: Adult; Anti-Inflammatory Agents; Betamethasone Valerate; Cell Division; Cells, Cultured; Chemotaxis; Desoximetasone; Fibroblasts; Glucocorticoids; Humans; Hydrocortisone; Middle Aged; Prednisolone