INTRACUTANEOUS TRANSPORT OF ORALLY-ADMINISTERED FLUCONAZOLE TO THE STRATUM-CORNEUM

Fluconazole administered at 150 mg/week for 1-5 weeks is effective ora lly against dermatophytes and yeast in stratum corneum. Clinical and m ycological cure rates approach 90%, but the precise distribution of th e drug within various layers of skin is uncertain. We administered flu conazole at 150 mg/week for 2 weeks to 5 volunteers. Distribution of f luconazole in biopsies of skin was imaged by energy dispersive analysi s of X-rays (EDX) and transmission electron microscopy, and in cells b y electron energy-loss spectroscopy (EELS). Eight hours after a second dose, EDX showed fluconazole highest and homogeneously distributed in stratum corneum, lower in the rest of the epidermis, and lowest in de rmis, The highest fluconazole levels detected by EELS were in cytoplas mic inclusions of sweat and sebaceous glands and less in keratinocytes and dermal collagen, We conclude that fluconazole delivered to stratu m corneum by direct diffusion from capillaries and in sweat is also in all likelihood transported in sebum.