Bioavailability of fluconazole in the skin after oral medication

Abstract

Fluconazole is an antimycotic drug which until now has been used mostly in the systemic therapy of yeast infections. We have now demonstrated the presence of this drug in various skin structures. After administration of 50 mg of fluconazole per day for 12 days to healthy volunteers, the following mean drug concentrations were measured: serum 1.81 micrograms ml-1, sweat 4.58 micrograms ml-1, dermis-epidermis (without stratum corneum) 2.77 micrograms g-1 and stratum corneum 73 micrograms g-1. Thus, 4 h after the last dose the antimycotic attains a 40-fold higher concentration in the stratum corneum than in serum. One week after ending the oral treatment, 5.8 micrograms g-1 fluconazole was present in stratum corneum. After daily ingestion of 200 mg of fluconazole for 5 days there was a further increase in the mean concentration of fluconazole in stratum corneum, to 127 micrograms g-1. Even 4-5 months after completing the oral treatment, fluconazole was detectable in the head hair and toenails of healthy volunteers. Fluconazole is eliminated from the stratum corneum about 2-3 times more slowly than from serum or plasma. After oral administration fluconazole evidently accumulated rapidly and intensively into the stratum corneum. The concentrations then attained or exceeded the in vitro minimal inhibitory concentrations of fluconazole for most of the dermatophytes and yeasts which are involved in cutaneous mycoses.