Deflazacort induced stronger immunosuppression than expected.

Prednisone (PDN) impairs cognitive functioning and brain structures in humans and animals. Deflazacort (DFZ) is a synthetic glucocorticoid claimed to have lesser side effects than prednisone. The objective of this study was to assess whether chronic administration (90 days) of DFZ produces less neuronal degeneration and glial reactivity than PDN. Male Swiss-Wistar rats were studied. Controls received 0.1 ml distilled water orally. The PDN group received prednisone 5 mg per kg per day orally, and the DFZ group received deflazacort 6 mg per kg per day orally. This model had to be assembled in three different occasions due to excess mortality in the DFZ group. A fourth model was assembled using only the DFZ group and slides of water and PDN-exposed rats from a previous study were used as comparators. The index of degenerated neurons and the number and cytoplasmic transformation of astrocytes and microglia cells were evaluated in the prefrontal cortex, CA1, and CA3 hippocampus. The results show that the overall mortality was 49% in the DFZ group, 4.5% in the PDN group, and none of the controls died. Routine necropsy showed infection in multiple organs. The PDN group had two times higher neuronal degeneration in the prefrontal cortex, almost 11 times in CA1, and four times in CA3 hippocampus when compared with controls and DFZ group. Astrocytes reactivity was increased in the PDN- and DFZ-exposed rats compared with controls. The DFZ group showed an average of four times less microgial cells in the three studied regions when compared with controls and the PDN group. In conclusion, it seems that DFZ at the equivalent licensed dose produced a stronger immunosuppressive effect--systemic and in brain tissue--than PDN, but induced less neuronal damage. The immunosuppressant magnitude of DFZ should be further studied in clinical settings.

Short courses of high-dose inhaled budesonide and serum IgG subclass levels in healthy volunteers.

BACKGROUND: The incidence of systemic side effects of inhaled budesonide increases at doses exceeding 2000 micrograms/day. OBJECTIVE: This study was carried out to investigate whether high-dose inhaled budesonide affects serum IgG subclass concentrations in healthy adult volunteers. METHODS: Two groups of 10 subjects each inhaled 2.4 mg of budesonide per day in a double-blind, crossover study of morning (8:00 AM and noon, group A) and diurnal (8:00 AM and 8:00 PM, group B) dosing schedules for 4 weeks each, separated by a 2-week washout period. The budesonide was inhaled through a pressurized metered-dose inhaler, mounted on a 750 ml Nebuhaler (ASTRA Pharmaceuticals, Lund, Sweden). The IgG subclass levels were determined at baseline and every 2 weeks until the end of the study period (10 weeks). RESULTS: There were no statistically significant changes in the serum IgG subclass concentrations over the 10-week study period in group A, group B, or groups A and B combined. CONCLUSION: Inhalation of budesonide, 2.4 mg/day, through a large-volume spacer for repeated 1-month periods does not influence serum IgG subclass concentrations in healthy adults, suggesting that budesonide does not cause systemic humoral immunosuppression when given at therapeutic doses.

Contact sensitivity and cross-reactivity of budesonide.

5 cases of allergic contact dermatitis due to budesonide are described. We studied the antigen determinant structures in these cases by applying patch tests with several substances related to budesonide. 2 cases showed cross-reactions to both amcinonide and prednisolone acetate. The antigen determinant structure is also discussed.