Pharmacokinetic investigation of oral itraconazole in stratum corneum level of tinea pedis.

Abstract

In the present study, the authors administered 100 mg itraconazole (ITCZ) twice daily for a period of 1 week to six patients with hyperkeratotic type tinea pedis, and examined its efficacy, safety profile, and usefulness. ITCZ concentration in stratum corneum was also measured to examine the mobility of the drug into the affected site of planta pedis. ITCZ concentration in the stratum corneum of the affected part was first detected at 1 week after the completion of administration, gradually increased over time, and peaked at 3 weeks, with the sum of ITCZ and hydroxyitraconazole (OH-ITCZ) amounting to 163.7 ng g(-1) on a average. It then gradually decreased to a total sum of 10.3 ng g(-1) on average at 8 weeks following the completion of administration. When compared with the geometric mean minimum inhibitory concentration (MIC) of ITCZ against fresh clinical isolates of dermatophytes (Trichophyton rubrum) (0.06 microg ml(-1)), the stratum corneum ITCZ concentration in this study was 2.1-fold of the geometric mean MIC at 2 weeks following the completion of administration, and 2.4-fold at 4 weeks. Although ITCZ does not produce therapeutic effectiveness (fungistasis) during the period of administration, it starts appearing at 2 weeks after the completion of administration, and after it peaks out at 3-4 weeks, clinical symptoms started improving. These results suggest that satisfying effects can be achieved in a short-term oral ITCZ at a dose of 100 mg twice daily for a period of 1 week in cases of hyperkeratotic type tinea pedis.