The antiinflammatory effects of ketoconazole
| Autor: | Geert Cauwenbergh, Frank C. Odds, Frans Van Gerven, Jan Van Cutsem, Paul A. J. Janssen |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
medicine.medical_specialty
Erythema Combination therapy business.industry Cholesterol Retinoic acid Dermatology Metabolism Pharmacology medicine.disease_cause chemistry.chemical_compound Endocrinology chemistry Staphylococcus aureus Internal medicine medicine Ketoconazole medicine.symptom business Hydrocortisone medicine.drug |
| Zdroj: | Journal of the American Academy of Dermatology. 25:257-261 |
| ISSN: | 0190-9622 |
| DOI: | 10.1016/0190-9622(91)70192-5 |
| Popis: | Several reports have demonstrated the efficacy of topical ketoconazole in dermatologic conditions that are not exclusively related to fungi. Some basic pharmacologic studies have indicated effects of ketoconazole on cholesterol production in keratinocytes, on the 5-lipoxygenase enzyme, and on the metabolism of all- trans -retinoic acid in the skin. These observations have led to the hypothesis that topically applied ketoconazole may possess antiinflammatory properties. This hypothesis was tested in an animal model in which living and killed Staphylococcus aureus applied to the backs of guinea pigs resulted in inflammation with erythema and hyperkeratosis. Ketoconazole 0.5% or 2% was applied topically once daily in an ointment base, either as monotherapy or in combination with hydrocortisone acetate 1%. In addition, untreated, excipient-treated, and hydrocortisone acetate-treated animals were included in the study design. All groups consisted of 10 animals that were observed and scored daily up to 3 days after the experimental therapy was stopped. In the animal model involving killed bacteria (i.e., no infection), topical ketoconazole had antiinflammatory activity comparable to that of hydrocortisone acetate. The activity of ketoconazole on the skin of animals infected with living bacteria (i.e., active bacterial infection) was superior to that of steroid therapy, which suggests some antibacterial effect of topically applied ketoconazole. The combination therapy was highly active under both conditions. These results suggest that, apart from the known antimycotic effects of ketoconazole, this molecule might also have effects against gram-positive bacteria at the high concentrations obtained after local application. In addition, the antiinflammatory potential suggested by the known inhibitory effect of ketoconazole on 5-lipoxygenase activity is confirmed in this animal model and seems comparable to that of weak steroids. Finally, in this study, some effects on keratinization were observed that might be explained by reported effects of ketoconazole on cholesterol production in keratinocytes or by the inhibitory effects of the molecule on endogenous all- trans -retinoic acid. |
| Databáze: | OpenAIRE |
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