抗真菌剤ＨＯＣ‐１５５クリームの反復大量塗布試験

Abstract

HOC-155 Cream is a topical antifungal formulation containing an imidazole derivative, omoconazole nitrate. The pharmacokinetics and safety of HOC-155 Cream in a repeated high dose were examined as a part of a phase I study in 6 healthy male volunteers aged 20 to 24 years. We applied 5 g of 1% HOC-155 Cream per day on the skin of subjects' back over 12 hours for 7 consecutive days. Of the six subjects studied, one subject had erythema and another had small eruptions on the skin where HOC-155 Cream had been applied. Both skin manifestations, which spontaneously disappeared with no treatment during the period of the study, were likely attributable to the primary irritation caused by the base in HOC-155 Cream in addition to the effects of covering the skin with gauze and local sweating. No effect attributable to HOC-155 Cream was observed in laboratory tests during the period of the study. The mean percutaneous absorption rate for HOC-155 Cream over 12 hours in each study day ranged from 14.5±1.8 (mean±SD, on the first day of application) to 10.8±1.9% of the dose applied to the skin. Neither omoconazole nitrate nor its principal metabolite (M1) was detected using GC-MS assay in serum samples taken from all subjects studied after the 7 consecutive days HOC-155 Cream application. Less than 0.1% of the omoconazole nitrate applied was excreted in the urine, mostly as a conjugated form of M1 with glucuronic acid. In conclusion, the safety of HOC-155 Cream applied in a repeated high dose was confirmed under the present study conditions and the mean percutaneous absorption rate for HOC-155 Cream was almost the same degree as that for other antifungal agents considering intersubject variability during the period that HOC-155 Cream was applied to the skin.