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Topical cyclosporine administration in rabbits
L M Stokar1, G J Burckart, M D'Souza
1Department of Dermatology, University of Pittsburgh, PA 15261.
Research Communications in Chemical Pathology and Pharmacology
|April 1, 1990
Summary
Topical cyclosporine (CyA) effectively suppressed skin reactions in rabbits, demonstrating localized immunosuppression. This study suggests topical CyA may offer a viable alternative for patients unable to take oral immunosuppressants.
Area of Science:
- Immunology
- Dermatology
- Pharmacology
Background:
- Cyclosporine (CyA) is a potent immunosuppressant with dose-limiting toxicities.
- Topical administration of CyA could localize immunosuppressive effects or provide an alternative route for patients with oral intolerance.
Purpose of the Study:
- To evaluate the potential for transdermal delivery of cyclosporine.
- To assess the localized versus systemic effects of topical CyA administration.
Main Methods:
- Rabbits were sensitized to dinitrochlorobenzene (DNCB).
- Topical application of 100 mg CyA or vehicle was administered.
- DNCB skin testing was repeated at the site of administration and a distal site at 15 and 28 days.
- Blood concentrations of CyA were monitored.
Main Results:
- CyA-treated rabbits showed significant suppression of DNCB reactions at both 15 and 28 days.
- Significant differences in DNCB reaction were observed between the topical administration site and a distal site.
- Topical CyA resulted in slow, variable absorption, but frequently achieved blood concentrations >1000 ng/ml.
Conclusions:
- Localized dermatologic immunosuppressive effects of CyA can be achieved through topical administration.
- High systemic blood concentrations of CyA are present after topical administration in this rabbit model.