Efficacy of oral fluconazole in tinea pedis of the hyperkeratotic type. Stratum corneum levels

Abstract

In this study, in addition to studying the efficacy and safety of the once-daily administration of 100-mg capsules of fluconazole over an 8-week administration period with six patients with hyperkeratotic-type tinea pedis, we also measured the serum and horny layer concentrations of fluconazole to study the mobility into the horny layer in diseased areas of the sole skin. The final overall efficacy and overall safety were both 100% (six out of six), and no side-effects, including abnormal laboratory changes, were observed in any of the patients. The drug mobility study revealed that in the horny layer of the skin a steady state was reached after 4 weeks of administration, with the mean concentration being 12.8 micrograms g-1. This concentration was a high concentration that was no less than 13 times the geometric mean MIC (0.972 microgram ml-1) for fresh clinical isolates of Trichophyton rubrum. Based on the above results, fluconazole is considered to be highly useful for treating various kinds of dermatomycosis, including hyperkeratotic-type tinea pedis.

Intracutaneous Distributions of Fluconazole, Itraconazole, and Griseofulvin in Guinea Pigs and Binding to Human Stratum Corneum

“…and the yeast Malassezia furfur), which cause fungal skin infections, generally colonize stratum corneum or keratinized adnexa and only very seldom penetrate into the cutis. Various yeasts, such as Candida albicans and Cryptococcus neoformans, can also penetrate into nonkeratinized epidermis and cutis (17,25). It is suggested that a high concentration of an antifungal agent is required to show sufficient efficacy against fungal skin infections not only in the stratum corneum but also in the epidermis-cutis.…”

“…The FLC concentrations in plasma and the abdominal stratum corneum were measured by a modification of the highperformance liquid chromatography (HPLC) method of Rex et al (14), and those in the skin tissue, the stratum corneum of planta pedis, and nail were determined by the HPLC method of Tanuma et al (17) as follows. The 2,4-dichloro homologue of FLC was synthesized and used as the internal standard (IS).…”

Usefulness and pharmacokinetic study of oral terbinafine for hyperkeratotic‐type tinea pedis

“…Tanuma et al. has reported that when fluconazole (FCZ) was administered at 100 mg day −1 for 8 weeks, its concentration in the stratum corneum of the affected sole lesions was stable at 4 weeks after initiating the treatment, averaging 12.8 μg g −1 = 12 800 ng g −1 , which is more than 13 times of the MIC, and then dropped down to 7.2 μg g −1 = 7200 ng g −1 at 1 week post‐treatment, and to 3.0 μg g −1 = 3000 ng g −1 at 5 weeks post‐treatment 7 …”

Usefulness and pharmacokinetic study of oral terbinafine for hyperkeratotic type tinea pedis

“…Tanuma et al. [2] reported that when fluconazole (FCZ) was administered at 100 mg day −1 for 8 weeks, its concentration in the stratum corneum of the affected sole lesions was stable at 4 weeks after initiating the treatment, averaging 12.8 μg g −1 = 12 800 ng g −1 , which is more than 13 times of the MIC, and then dropped down to 7.2 μg g −1 = 7200 ng g at 1 week post‐treatment, and to 3.0 μg g −1 = 3000 ng g −1 at 5 weeks post‐treatment 7 …”

“…As hyperkeratotic type tinea pedis creates remarkable keratinization, topically applied antifungals do not penetrate the stratum corneum deep enough. Therefore, antifungal treatment is often unsuccessful when topical antifungal is used alone 1–4 . For this reason, oral antifungals such as griseofulvin (GRF) have long been prescribed as the first choice of drug to treat this disease 4 …”