latoconazole and liranaftate

The minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) of luliconazole against Trichophyton rubrum (14 strains) and Trichophyton mentagrophytes (14 strains), which are the most common cause of tinea, were compared with those of 6 topical antifungal drugs of lanoconazole, bifonazole, efinaconazole, liranaftate, naftifine and terbinafine.　Luliconazole showed the most potent antifungal activity (MIC90 =0.00098 μg/ml and MFC90 =0.0078 μg/ml) among the compounds tested against the two species. Efinaconazole and bifonazole, the drug of azole-class, showed a large MFC/MIC ratio. On the other hand, these ratios of luliconazole and lanoconazole were as small as those of liranaftate, naftifine and terbinafine which are thought to possess fungicidal mechanism. These results suggest that luliconazole possesses fungicidal activity against both species of Trichophyton.　In this study, we found that luliconazole had the most potent antifungal activity among the major topical antimycotics used in Japan and the US. Luliconazole would be the best-in-class drug for dermatophytosis in clinics.

Topics: Allylamine; Antifungal Agents; Drug Resistance, Fungal; Imidazoles; Microbial Sensitivity Tests; Naphthalenes; Pyridines; Terbinafine; Thiocarbamates; Triazoles; Trichophyton

The fungicidal activities of thiocarbamate antifungal agent liranaftate were studied by determining the MIC and the MCC against Trichophyton rubrum with the Milliflex -100 Test System and by determining the time-kill curve in comparison to that of six reference agents. Liranaftate and lanoconazole both showed excellent fungistatic activity against the conidia of T. rubrum. For each of these agents, the MIC after 14 days of contact was 0.009 g/ml. The liranaftate-induced decrease in the MCC occurred from 9 days onwards; MCC at 14 days was 0.039 g/ml. The MCC for tolciclate was also reduced from 9 days onwards, but that of amorolfine, lanoconazole, neticonazole, clotrimazole and bifonazole was not lowered up to 14 days. Similar results were obtained when the studies were performed with germinated conidia. The time-kill curves showed that both liranaftate and tolciclate, at concentrations ranging from 2 to 32 times the MICs, achieved a decrease in viable counts to below the detection limit within 7 to 9 days. In experiments with low levels of inoculum, only amorolfine produced a decrease to below the detection level, and that occurred at 14 days; no reduction in viable counts was observed up to 14 days with the four azole agents. Our data suggest that antifungal agents of the thiocarbamate class possess the most potent fungicidal activity against dermatophytes; these are followed in order by morpholine and azole antifungals.

Topics: Antifungal Agents; Drug Resistance, Fungal; Heterocyclic Compounds; Imidazoles; Microbial Sensitivity Tests; Morpholines; Naphthalenes; Pyridines; Thiocarbamates; Time Factors; Trichophyton