[Retention of ketoconazole in the skin following oral treatment]

Up to now there have been no data on how long ketoconazole is retained in the skin after administration has been discontinued. In our study, 17 probands received 200 mg ketoconazole daily for 10 days. Shave biopsies were taken from the buttocks on the last treatment day as well as 5 and 10 days later. Ketoconazole concentrations were determined by high-pressure liquid chromatography after extensive homogenization of the skin specimens. At the end of the treatment period, about 2 h after intake of the last tablet a median ketoconazole skin concentration of 3.6 micrograms/g was determined. Five days after the end of treatment, the median ketoconazole skin level was 2.5 micrograms/g and after 10 days it was still 1.2 micrograms/g. Using a bioassay with Candida albicans strain ATCC 28,516, no demonstrable amount of ketoconazole could be seen in the hair roots and adjacent hair shafts at days 10, 15 and 20 of the trial. These results suggest that ketoconazole reaches the horny layer by passive diffusion and that it is strongly adsorbed by keratin. Clinical experience indicates that repeated short-term treatment with ketoconazole provides an effective prophylaxis against the recurrence of superficial mycosis; our results represent experimental confirmation of this experience.