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Oral Fluconazole Concentrates in Stratum Corneum
None of the azole antifungals (ketoconazole, fluconazole, or itraconazole) have been approved for oral treatment of dermatomycoses. Although there have been many studies of azole dosing schedules for treating these infections, the best dosing schedule has yet to be determined.
This study of the distribution of orally administered fluconazole measured levels of the drug in the stratum corneum, epidermis-dermis (without stratum corneum), eccrine sweat, and serum in 33 men given dosages of either 50 mg daily for 12 days or 150 mg once weekly for 2 weeks. High fluconazole concentrations were found in the stratum corneum with both dosing schedules. With the daily schedule, the fluconazole concentration in the stratum corneum was 73.0 µg on the last day of treatment and 5.8 µg 7 days after treatment ended. With the weekly dosage, the concentration was 7.1 µg 7 days after the second dose. High concentrations were also found in sweat and epidermis-dermis (2.93 to 4.62 µg), and were all well above the concentrations in serum.
Comment: Dermatomycoses begin as infections of the stratum corneum. Agents used to treat dermatomycoses must be delivered to the stratum corneum either through topical or parenteral administration. Fluconazole accumulates in the stratum corneum by direct diffusion through the epidermis-dermis and through excretion of sweat. Given that fluconazole is effective in treating yeast and dermatophyte infections in concentrations as low as 0.04 µg, the levels achieved by oral administration in both the daily and weekly dosage schedules appear to be effective.
— Johnson
Published in Journal Watch Dermatology June 1, 1993
Citation(s):
Faergemann J, Laufen H. Levels of fluconazole in serum, stratum corneum, epidermis-dermis (without stratum corneum), and eccrine sweat. Clin Exp Dermatol 1993 18 102-106.
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