clobetasol and Body-Weight

Topical corticosteroids such as hydrocortisone-17-butyrate (HCB) and clobetasol-17-propionate (CP) and vitamin D(3) derivatives such as calcipotriol (CAL) are widely used to treat psoriasis. The immunosuppressive effects of corticosteroids make their topical use a concern for skin carcinogenicity. Few studies have assessed the effect of topical corticosteroids and topical vitamin D(3) derivatives on photocarcinogenesis induced by ultraviolet radiation. We investigated whether HCB, CP, or CAL can accelerate photocarcinogenesis using simulated solar radiation (SSR). HCB, CP, or CAL was applied topically to the backs of hairless, female, C3.Cg/TifBomTac-immunocompetent mice in 16 groups of 25 mice each. The drugs were applied three times weekly followed by 0, 2, 4, or 6 standard erythema doses (SED) of SSR for 365 days or until death. No change was observed in the time required for tumor development in mice treated with HCB and 2 SED (HCB-2SED) and HCB-6SED. However, the time required for tumor development increased with HCB-4SED treatment. Treatment with CP-2SED did not change the time to onset of the first and second tumor, but all other CP treatments in combination with SSR increased the time. CAL-2SED decreased the time to onset of the first tumor but not of the second and third tumor. CAL-4SED and CAL-6 SED did not change or increased the time to tumor development. Our data indicated that topical administration of HCB and CAL did not alter the photocarcinogenesis of SSR and that topical CP administration had a photoprotective effect. Thus, HCB, CP, and CAL do not increase photocarcinogenesis induced by SSR.

Topics: Administration, Topical; Animals; Body Weight; Calcitriol; Carcinoma, Squamous Cell; Clobetasol; Dermatologic Agents; Female; Hydrocortisone; Kaplan-Meier Estimate; Mice; Mice, Hairless; Neoplasms, Radiation-Induced; Skin; Skin Neoplasms; Skin Pigmentation; Sunlight; Ultraviolet Rays

Acute and subacute toxicities of clobetasone-17-butyrate, a new anti-inflammatory corticosteroid, were studied in mice and rats. In the acute toxicity tests intraperitoneal LD50 values of the drug were estimated to be around 5 g/kg for both sexes of mice, 1.51 g/kg for male and 1.66 g/kg for female rats. Subcutaneous and oral administration induced no fatal cases at dose of 3.6 (mice, s.c.), 2.6 (rats, s.c.) and 6.0 g/kg (mice and rats, p.o.). As for the toxic signs in both mice and rats after the i.p. and s.c. administrations, emaciation was marked, and atrophy of thymus, spleen and adrenals were observed. No marked symptoms, however, were induced in animals administered orally. In the subacute toxicity tests male and female rats were subcutaneously administered with the drug at daily doses of 0.01, 0.03, 0.1, 1.0, 10 and 100 mg/kg for one month. Dose dependent symptoms such as suppression in body weight gain, emaciation, regressive changes in adrenal, lymphatic and hematopoietic tissues, decrease in circulating white blood cell and lymphocyte counts, and increase in total cholesterol level of serum were induced in the rats administered at 0.1 mg/kg/day and more than that, indicating that the maximum nontoxic dose in this experimental condition was 0.03 mg/kg/day. In recovery tests it was observed that the rats, which had been administered with the drug at 1.0 mg/kg/day for one month, were almost normal two months after the final administration.

Topics: Administration, Oral; Adrenal Cortex Hormones; Animals; Anti-Inflammatory Agents; Betamethasone; Body Weight; Clobetasol; Female; Injections, Intraperitoneal; Injections, Subcutaneous; Lethal Dose 50; Male; Mice; Organ Size; Rats

Different concentrations of butyl 6alpha-fluoro-11beta-hydroxy-16alpha-methyl-3,20-dioxo-1,4-pregnadien-21-oate (fluocortin butylester FCB, Vaspit) and of clobetasone-17-butyrate, clobetasole-17-propionate and hydrocortisone-17-butyrate have been administered topically in order to investigate dermal and systemic side effects. It could be shown that FCB exhibits by far the least side effects. A specially devised apparatus covering the site of substance application, guaranteed an exclusive dermal absorption. Side effects, therefore, cannot be ascribed to oral ingestion of the drugs.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Body Weight; Clobetasol; Fluocortolone; Hydrocortisone; Kidney; Male; Organ Size; Pregnadienediols; Rats; Skin; Skin Physiological Phenomena; Spleen; Tensile Strength; Thymus Gland