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Activity of the triazole antifungal r126638 as assessed by corneofungimetry
C Piérard-Franchimont1, J Ausma, L Wouters
1Department of Dermatopathology, University Hospital of Liège, Liège, Belgium.
Background:
R126638 is a novel triazole exhibiting potent in vitro and in vivo antifungal activity against fungal pathogens including dermatophytes and yeasts.
Objective:
To determine the antifungal activity in time in the stratum corneum of healthy volunteers after oral intake of R126638 at a daily dose of 100 or 200 mg for 1 week.
Method:
Sixteen male volunteers were randomly allocated to oral treatment with either 100 or 200 mg of R126638 once daily for 1 week. Five cyanoacrylate skin surface strippings (CSSS) were obtained from the forearm of each subject before drug intake at day 1. CSSS were also collected during treatment at day 2 (24 h after the first drug intake, before the second drug intake), at day 4 (before the fourth drug intake) and at day 7 (10 h after the last drug intake). The post-treatment lingering effect was assessed at day 10 (3 days after treatment) and at day 14 (7 days after treatment). The corneofungimetry bioassay was performed on these CSSS to assess the antifungal profile of R126638. Cells of different fungal species (Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis, Candida albicans and Malassezia globosa) were deposited and cultured for 10 days on CSSS in a sterile and controlled environment. The extent of fungal growth on the stratum corneum was determined using computerized image analysis.
Results:
R126638 clearly reduced the growth of all tested fungal species. The onset of effects of R126638 was evidenced at day 4 when it reached statistical significance for 3 of 5 species. At day 7, significance was reached for 4 of 5 species. During the posttreatment period, R126638 remained effective for 4 of 5 species at day 10, and this activity persisted until day 14 for 2 of 5 species.
Conclusion:
A broad spectrum antifungal activity was rapidly expressed in the stratum corneum after oral intake of R126638. The drug likely reached the upper layers of the stratum corneum by diffusion and persisted in this location for at least 7 days after treatment.
Insights
R126638 demonstrated potent antifungal activity in the stratum corneum after oral administration. This novel triazole showed rapid onset and sustained antifungal effects against common fungal pathogens for up to 14 days post-treatment.
Area of Science:
- Dermatology
- Mycology
- Pharmacology
Background:
- R126638 is a novel triazole with demonstrated in vitro and in vivo antifungal properties.
- It is effective against key fungal pathogens, including dermatophytes and yeasts.
Purpose of the Study:
- To evaluate the time-dependent antifungal activity of R126638 within the stratum corneum.
- To assess the drug's efficacy after oral administration in healthy volunteers.
Main Methods:
- Healthy male volunteers received oral R126638 (100 or 200 mg daily) for one week.
- Stratum corneum samples were collected via cyanoacrylate skin surface strippings (CSSS) at multiple time points.
- Corneofungimetry bioassays were performed on CSSS using five fungal species to quantify antifungal activity.
Main Results:
- R126638 significantly reduced the growth of all tested fungal species.
- Statistically significant antifungal effects were observed by day 4, with improvement by day 7.
- Antifungal activity persisted in the stratum corneum for up to 14 days after treatment cessation.
Conclusions:
- Oral R126638 rapidly exerts broad-spectrum antifungal activity in the stratum corneum.
- The drug likely penetrates the upper stratum corneum via diffusion.
- Sustained antifungal presence in the stratum corneum was observed for at least 7 days post-treatment.
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