Studies on the antifungal activity of the new imidazole antimycotic lanoconazole in infected sites. Distribution in the skin and in vitro activity in the presence of stratum corneum
Niwano, Y.; Matsui, M.; Tabuchi, T.; Kanai, K.; Hamaguchi, H.; Miyazaki, T.; Uchida, K.; Yamaguchi, H.
Arzneimittel-Forschung 47(9): 1056-1060
1997
ISSN/ISBN: 0004-4172 PMID: 9342423 Document Number: 474411
The distribution of lanoconazole within the dorsal skin of rats was examined by measurement of radioactivity and microscopic autoradiography. 24 h after dermal application of [14C]lanoconazole cream formulation, 83% of the total radioactivity in the skin was recovered from the stratum corneum, and thereafter the radioactivity decreased gradually up to 96 h. Metabolite analysis showed that >94% of the extractable radioactivity was lanoconazole after 24 and 48 h. Microautoradiograms of the skin also supported the radioactivity distribution. Candida albicans TIMM 2640 was incubated for 10 days at 27 degrees C in a vitamin-supplemented yeast carbon base medium containing 5 mg/ml of human stratum corneum and different concentrations of lanoconazole or bifonazole. Compared with the control culture, lanoconazole strongly inhibited fungal growth in a concentration dependent manner at concentrations >0.1 micro g/ml, resulting in a reduction of viable cell recovery to <50% after 10 days. The inhibitory activity of bifonazole was clearly weaker than that of lanoconazole. At concentrations of 0.1-10.0 micro g/ml lanoconazole reduced keratinolytic acid proteinase activity in the culture-supernate to 40-70% of the control value, while bifonazole showed 50% reduction of the activity at a concentration of 10.0 micro g/ml. It is concluded that lanoconazole is mainly distributed and retained in the stratum corneum after topical application where it exerts strong antifungal activity.