Levels of itraconazole in skin blister fluid after a single oral dose and during repetitive administration.
Oral itraconazole is effective in the treatment of mycoses. To measure its concentrations in the tissue, levels of total and non-protein-bound itraconazole were determined in serum, suction-induced blister fluid, and cantharides-induced blister fluid. Six healthy subjects received 200 mg as a single dose, followed by 100 mg/day for 10 days. Itraconazole binding in suction-induced blister fluid (99.54%) and cantharides-induced blister fluid (99.77%) was calculated from plasma protein binding (99.8%). The single-dose study showed the drug levels in blister fluid to increase more slowly than those in serum. The terminal half-life of itraconazole in serum was 22.5 +/- 3.2 hours. Suction- and cantharides-induced blister fluid levels declined in parallel. After the final dose, itraconazole penetration into cantharides-induced blister fluid was only 70%. Moreover, trough levels of unbound itraconazole in suction- and cantharides-induced blister fluid were 0.239 +/- 0.115 and 0.334 +/- 0.101 ng/ml and thus were significantly lower than free itraconazole levels in serum (0.422 +/- 0.125 ng/ml). Thus a distribution equilibrium between serum and blister fluids was not obtained. Free drug concentrations in suction- and cantharides-induced blister fluid were far lower than the minimal inhibitory concentration values for Candida ssp. and dermatophytes.
Schäfer-Korting
M
M
Pharmakologisches Institut für Naturwissenschaftler, Johann Wolfgang-Goethe Universität, Frankfurt, FRG.
Korting
H C
HC
Lukacs
A
A
Heykants
J
J
Behrendt
H
H
D000284:Administration, Oral; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001768:Blister / Q000378:metabolism*; D005260:Female; D006801:Humans; D017964:Itraconazole; D007654:Ketoconazole / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D013997:Time Factors
D000935:Antifungal Agents; D017964:Itraconazole; D007654:Ketoconazole