Activity of the Triazole Antifungal R126638 as Assessed by Corneofungimetry

Abstract

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.

A Pilot Study on Seborrheic Dermatitis Using Pramiconazole as a Potent Oral Anti-<i>Malassezia</i> Agent

“…The antifungal activity which was already demonstrated for pramiconazole in animals and humans [24,25,26,27] is confirmed in this study. With a single 200-mg pramiconazole dosing, seborrheic dermatitis improved dramatically.…”

“…This method is specifically designed for assessing the antifungal activity of a drug on fungi growing on human stratum corneum. Corneofungimetry was performed on 5 fungal species (Candida albicans, Malassezia globosa, Microsporum canis, Trichophyton rubrum, T. mentagrophytes) at different time intervals during and after 1 week of oral dosing with 100 or 200 mg of pramiconazole [27]. The drug clearly reduced the fungal growth of all strains on day 7.…”

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“…This diversity was recently linked with gene polymorphisms that may modulate the levels of circulating adhesion molecules and differentiate low and high levels in HD patients [19]. …”

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