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Development of glucocorticosteroids with enhanced ratio between topical and systemic effects
A Thalén1, R Brattsand, P H Andersson
1Research and Development Department, AB Draco, Lund, Sweden.
Acta Dermato-Venereologica. Supplementum
|January 1, 1989
Summary
Budesonide, a novel glucocorticosteroid, offers superior topical anti-inflammatory effects with fewer systemic side effects. Its unique structure enhances efficacy and safety compared to existing treatments.
Area of Science:
- Pharmacology
- Medicinal Chemistry
Background:
- Glucocorticosteroids are vital for anti-inflammatory therapy.
- Achieving high topical potency with minimal systemic side effects is a key therapeutic goal.
Purpose of the Study:
- To develop novel 16,17-acetal glucocorticosteroids with an improved topical/systemic activity ratio.
- To evaluate the anti-inflammatory and systemic effects of these new compounds, particularly budesonide.
Main Methods:
- Synthesis and evaluation of non-symmetric 16,17-acetals and fluorinated glucocorticosteroids in rodents.
- Comparison of topical anti-inflammatory potency and systemic side effects (cortisol levels) in human volunteers.
- In vitro assessment of budesonide's hepatic biotransformation rate.
Main Results:
- Non-symmetric 16,17-acetal substitution enhanced topical activity more than systemic activity.
- Budesonide demonstrated the highest topical/systemic activity ratio, outperforming triamcinolone acetonide and beclomethasone dipropionate.
- Budesonide showed similar topical potency to beclomethasone dipropionate but with significantly fewer systemic effects in volunteers.
- Budesonide is rapidly metabolized in the liver to less potent metabolites.
Conclusions:
- Novel 16,17-acetals represent a promising class of glucocorticosteroids for anti-inflammatory therapy.
- Budesonide exhibits a superior therapeutic profile due to its enhanced topical efficacy and reduced systemic side effects.
- Rapid hepatic metabolism contributes to budesonide's favorable safety profile.