Dermo-epidermal distribution of ketoconazole in man

: The dermo-epidermal distribution of ketoconazole was studied in 50 patients with fungal dermatoses by simultaneously determining drug concentrations in plasma and suction liquid (SL) obtained by dermo-epidermal separation. Fifteen patients were treated with a single 200-mg dose of ketoconazole while the remaining 35 underwent chronic treatment with 200 mg ketoconazole per day. In the single-dose study, ketoconazole SL concentrations determined between 80 and 390 min showed mean peak values of 0.74 +/- 0.53 micrograms/ml at intermediate sampling times of about 180 min. The maximum mean plasma concentration of 2.37 +/- 1.26 micrograms/ml occurred at an intermediate sampling time (141 min) as well. In those patients receiving chronic treatment from 1 to 7 days, the mean plasma and SL concentrations were 1.07 +/- 1.17 micrograms/ml and 0.08 +/- 0.2 micrograms/ml, respectively, while chronic treatment from 15 to 64 days resulted in higher values of 2.22 +/- 1.91 micrograms/ml and 0.56 +/- 0.57 micrograms/ml, respectively. These results suggest that rapid and considerable passive diffusion of ketoconazole could take place during its transfer from the blood to the skin.