neticonazole and latoconazole

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

We developed a new technique for culture study that successfully recovers fungi from drug-treated skin tissues, in which tissue specimens were homogenized, dialyzed against water, digested with trypsin, and then washed with PBS, to eliminate the drug that remaining in the skin tissue specimens. With this modified culture method, we reevaluated the efficacy of KP-103, neticonazole, and lanoconazole in a guinea pig interdigital tinea pedis model. Guinea pigs with tinea pedis were topically treated with a 1% solution of KP-103 or a reference drug once a day for 10 consecutive days. Five days after the last treatment, left and right feet were subjected to culture study by the conventional and modified recovery culture methods, respectively. One hundred percent (20/20) of lanoconazole-treated feet were judged as culture-negative by the conventional culture method, but 85% (17/20) of the feet were shown to be culture-positive when the modified recovery culture method was used. On the other hand, KP-103 achieved high rates of culture-negative rates, 95% (19/20) and 85% (17/20), in both conventional and modified culture methods, respectively. Furthermore, on day-30 posttreatment, KP-103 sterilized 14 of the 20 infected feet, whereas neticonazole and lanoconazole were not effective even in reducing fungal burden. KP-103 proved to be highly effective in achieving mycological cure and preventing relapse against tinea pedis presumably because of its good bioavailability in the skin based on its low keratin-affinity, along with its potent antifungal activity.

Topics: Animals; Antifungal Agents; Colony Count, Microbial; Culture Media; Drug Evaluation, Preclinical; Guinea Pigs; Heterocyclic Compounds; Imidazoles; Male; Microbial Sensitivity Tests; Models, Animal; Time Factors; Tinea Pedis; Treatment Outcome; Triazoles; Trichophyton

Topics: Aged; Antifungal Agents; Dermatitis, Allergic Contact; Drug Hypersensitivity; Drug Therapy, Combination; Foot Dermatoses; Heterocyclic Compounds; Humans; Imidazoles; Male; Ointments