Levels of fluconazole in serum, stratum corneum, epidermis-dermis (without stratum corneum) and eccrine sweat

Abstract

The distribution in the skin of orally active antifungals and other drugs claimed to be active in the treatment of skin diseases is of major importance, but to date has been studied only rarely. In the present study the distribution of fluconazole in stratum corneum, epidermis-dermis (without stratum corneum), eccrine sweat and serum was studied in human male volunteers after dosages of 50 mg daily for 12 days and 150 mg once weekly for 2 weeks. In the present study high levels of fluconazole were found especially in the stratum corneum. At a dose of 50 mg once daily the concentration of fluconazole after 12 days was 73.0 micrograms/g and 7 days after cessation of treatment the concentration was still 5.8 micrograms/g. At the 150 mg once a week dose the concentration 7 days after the second dose was still 7.1 micrograms/g in stratum corneum indicating that medication once a week may be effective in the treatment of dermatomycoses. High concentrations, all above the serum concentrations, were also seen in sweat and epidermis/dermis. These results indicate that fluconazole is delivered to the stratum corneum, where it is accumulated, through sweat and by direct diffusion through the dermis-epidermis. These pharmacokinetic results indicate that the drug should be very effective in the treatment of dermatomycoses. An extremely high concentration of the drug in the stratum corneum combined with concentrations from 2.93 to 4.62 micrograms/g in the rest of the epidermis and dermis is important in the treatment of these diseases.

Tissue Penetration of Antifungal Agents

“…Fluconazole concentrations within the dermis are similar to those in plasma (216,217), but concentrations in the stratum corneum are up to 40 times those in plasma (217,218) (Fig. 7).…”

“…7). The clearance of fluconazole from the stratum corneum is also significantly slower than that from the plasma and other skin layers, with concentrations that decline 2 to 3 times more slowly than the plasma concentrations (215,217,218). Interestingly, once-weekly oral dosing of 150 mg for 2 weeks results in higher fluconazole concentrations in the stratum corneum relative to those in the epidermis/dermis, sweat, and serum than those obtained by daily dosing at 50 mg for 12 days (217).…”

Topical terbinafine in the treatment of cutaneous leishmaniasis: triple blind randomized clinical trial

“…This drug is a lipophilic allylamine compound. terbinafine penetrates keratinized tissues, and enters the stratum corneum and sebum by direct diffusion through the dermis and living epidermis (Faergemann 1997, Faergemann et al 1990). …”

Development of terbinafine solid lipid nanoparticles as a topical delivery system

“…31 Thus, ACP1-GM1 with particle size of 233.0 nm should have the ability to form an occlusive film on the surface of skin, increase the hydration of SC, and improve the permeation of terbinafine into skin. This indicated that the application of ACP1-GM1 for 12 …”

“…7,8 Moreover, the TB treatment duration is shorter in most cases. 9,10 Based on several clinical studies conducted in humans [11][12][13] and animals, 14,15 it was noted that TB accumulates in the skin and persists at high concentrations for up to several weeks after discontinuing drug application. The superior efficacy of TB after the end of the treatment period is attributed to its fungicidal effect in addition to the favorable pharmacokinetic characteristics of substantial and rapid penetration into the stratum corneum (SC), where it remains in the skin for a long time after discontinuing treatment.…”