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Combination of amorolfine with various antifungal drugs in dermatophytosis
1F. Hoffmann-La Roche Ltd, Pharma Division, Basel, Switzerland.
Abstract:
The fungistatic activity of ketoconazole, griseofulvin and terbinafine alone and in combination with amorolfine was tested in casitone agar. The fungistatic activity of all three against Trichophyton mentagrophytes is slightly increased by the addition of amorolfine. In yeasts the results are not so clear. The combinations of amorolfine with griseofulvin, terbinafine, itraconazole and fluconazole were always more efficient in a murine model of dermatophytosis than the monotherapy, thus a clear synergism between amorolfine and other antifungals was seen.
Insights
Amorolfine enhances the fungistatic activity of ketoconazole, griseofulvin, and terbinafine against Trichophyton mentagrophytes. Combinations of amorolfine with other antifungals demonstrated clear synergism in treating fungal infections in mice.
Area of Science:
- Mycology
- Pharmacology
- Dermatology
Background:
- Fungal infections, particularly dermatophytosis, pose a significant health challenge.
- Existing antifungal monotherapies can face limitations in efficacy.
- Investigating combination therapies is crucial for improving treatment outcomes.
Purpose of the Study:
- To evaluate the fungistatic activity of ketoconazole, griseofulvin, and terbinafine alone and in combination with amorolfine.
- To assess the synergistic potential of amorolfine with other antifungal agents in a preclinical model.
Main Methods:
- Antifungal susceptibility testing of ketoconazole, griseofulvin, terbinafine, and amorolfine using casitone agar.
- In vivo efficacy evaluation of combination antifungal therapies in a murine model of dermatophytosis.
Main Results:
- Amorolfine slightly enhanced the fungistatic activity of ketoconazole, griseofulvin, and terbinafine against Trichophyton mentagrophytes in vitro.
- Combinations of amorolfine with griseofulvin, terbinafine, itraconazole, and fluconazole showed significantly greater efficacy than monotherapy in a murine model.
- Clear synergistic effects were observed for amorolfine in combination with other tested antifungals in vivo.
Conclusions:
- Amorolfine exhibits synergistic activity when combined with other antifungal drugs, suggesting potential for enhanced treatment of dermatophytosis.
- Combination therapy involving amorolfine may offer a more effective strategy for managing fungal skin infections compared to monotherapy.