The in vitro activity of
KP-103, a novel
triazole derivative, against pathogenic fungi that cause
dermatomycoses and its therapeutic efficacy against plantar
tinea pedis and
cutaneous candidiasis in guinea pigs were investigated. MICs were determined by a broth microdilution method with morpholinepropanesulfonic
acid-buffered RPMI 1640 medium for Candida species and with Sabouraud
dextrose broth for dermatophytes and by an
agar dilution method with medium C for Malassezia furfur.
KP-103 was the most active of all the drugs tested against Candida albicans (geometric mean [GM] MIC, 0.002 microg/ml), other Candida species including Candida parapsilosis and Candida glabrata (GM MICs, 0.0039 to 0.0442 microg/ml), and M. furfur (GM MIC, 0.025 microg/ml).
KP-103 (1%
solution) was highly effective as a treatment for guinea pigs with
cutaneous candidiasis and achieved mycological eradication in 8 of the 10 infected animals, whereas none of the
imidazoles tested (1% solutions) was effective in even reducing the levels of the infecting fungi.
KP-103 was as active as
clotrimazole and
neticonazole but was less active than
lanoconazole and
butenafine against Trichophyton rubrum (MIC at which 80% of isolates are inhibited [MIC(80)], 0.125 microg/ml) and Trichophyton mentagrophytes (MIC(80), 0.25 microg/ml). However,
KP-103 (1%
solution) exerted therapeutic efficacy superior to that of
neticonazole and comparable to those of
lanoconazole and
butenafine, yielding negative cultures for all samples from guinea pigs with plantar
tinea pedis tested. This suggests that
KP-103 has better pharmacokinetic properties in skin tissue than the reference drugs. Because the in vitro activity of
KP-103, unlike those of the reference drugs, against T. mentagrophytes was not affected by hair as a keratinic substance, its excellent therapeutic efficacy seems to be attributable to good retention of its antifungal activity in skin tissue, in addition to its potency.