[Show abstract][Hide abstract] ABSTRACT: Luliconazole is a novel topical antifungal imidazole with broad-spectrum and potent antifungal activity. The drug is under clinical development in the United States for management of dermatophytosis with a short-term treatment regimen. The present study was undertaken to investigate the clinical benefit of short-term therapy with luliconazole cream in guinea pig models of tinea corporis and tinea pedis induced with Trichophyton mentagrophytes. The dose-dependent therapeutic efficacy of topical luliconazole cream (0.02 to 1%), measured by macroscopic improvement of skin lesions and by fungal eradication as determined by a culture assay, was demonstrated using a tinea corporis model. The improvement in skin lesions seen with luliconazole cream was observed even at a concentration of 0.02%, and its efficacy at 0.1% was equal to that of 1% bifonazole cream. The efficacy of short-term therapy with 1% luliconazole cream, which is used for clinical management, was investigated using the tinea corporis model (4- and 8-day treatment regimens) and the tinea pedis model (7- and 14-day treatment regimens). The 1% luliconazole cream completely eradicated the fungus in half or less of the treatment time required for 1% terbinafine cream and 1% bifonazole cream, as determined by a culture assay for both models. These results clearly indicate that 1% luliconazole cream is sufficiently potent for short-term treatment for dermatophytosis compared to existing drugs. Luliconazole is expected to be useful in the clinical management of dermatophytosis.
Antimicrobial Agents and Chemotherapy 03/2012; 56(6):3138-43. · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tinea corporis and the tinea pedis model in guinea pig with Trichophyton mentagrophytes are well established models of dermatophytoses. We attempted to provide animal infection models for T. tonsurans, endemic in Japan, and Malassezia restricta, an important pathogenic factor in seborrhoeic dermatitis, by utilizing the tinea corporis model. An inoculum of the organisms was applied to the back skin of male guinea pigs. T. tonsurans infected animals showed follicular inflammation mimicking those seen in humans. Interestingly, anthropophilic T. tonsurans showed a high infection rate in animal skin. Meanwhile, a single application of M. restricta, as well as consecutive applications to the surface of the skin without any pretreatment, succeeded in producing scales mimicking seborrhoeic dermatitis, but application of the pathogens after the tape stripping of the stratum corneum failed to induce infection. These models using guinea pigs were considered to be useful for studying the pathogenesis of, and evaluating therapies for, T. tonsurans infection and seborrhoeic dermatitis.
[Show abstract][Hide abstract] ABSTRACT: Luliconazole is a topical antifungal drug newly developed in Japan. The present study compares the in vitro antifungal activity of luliconazole against clinically important dermatomycotic fungi with that of other representative antifungal drugs. The reference drugs chosen were five classes of nine topical agents, i.e., allylamine (terbinafine), thiocarbamate (liranaftate), benzylamine (butenafine), morpholine (amorolfine), and azole (ketoconazole, clotrimazole, neticonazole, miconazole and bifonazole). The minimum inhibitory concentrations (MIC) of luliconazole and the reference drugs against Trichophyton spp. (T. rubrum, T. mentagrophytes and T. tonsurans) and Candida albicans were measured by the standardized broth microdilution method. Luliconazole demonstrated greater potency against Trichophyton spp. (MIC range: <or=0.00012-0.002 microg/ml) than the reference drugs, with T. rubrum being the most susceptible to it. Luliconazole was also highly active against Candida albicans (MIC range: 0.031-0.13 microg/ml), proving to be more potent than terbinafine, liranaftate, butenafine, amorolfine, and bifonazole, but less than ketoconazole, clotrimazole, neticonazole, and miconazole. Further, the MIC of luliconazole against Malassezia restricta, an important pathogenic agent involved in seborrhoeic dermatitis, was very low (MIC range: 0.004-0.016 microg/ml) suggesting action comparable to or stronger than that of ketoconazole. These results indicate a possible clinical role for luliconazole with its broad-spectrum antimycotic activity.
Medical mycology: official publication of the International Society for Human and Animal Mycology 01/2009; 47(6):640-7. · 2.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The in vitro antifungal activity of luliconazole, a novel topical imidazole, against pathogenic fungi implicated in dermatomycoses was studied. A total of 91 clinical isolates, consisting of 59 Trichophyton rubrum isolates, 26 T. mentagrophytes isolates, 1 Epidermophyton floccosum isolate, and 5 Candida albicans isolates were tested by the broth microdilution method, employing lanoconazole, terbinafine, and bifonazole as reference drugs. The minimum inhibitory concentrations (MICs) of luliconazole against T. rubrum and T. mentagrophytes were in the range of 0.00012-0.004 microg/ml and 0.00024-0.002 microg/ml, respectively. The MIC90 of luliconazole for these two species of dermatophytes was the same, at 0.001 microg/ml, and these values were 4 times, 30 times, and more than 1000 times lower than those of lanoconazole, terbinafine, and bifonazole, respectively. Similarly, the 1 isolate of E. floccosum tested was inhibited by luliconazole with an MIC of 0.001 microg/ml. Luliconazole also proved to be very potent against C. albicans (MIC range, 0.031-0.25 microg/ml), nearly on par, in terms of efficacy, with lanoconazole (0.063-0.25 microg/ml) and more potent than terbinafine (2->64 microg/ml) and bifonazole (0.5-4 microg/ml). These results showed that luliconazole was very potent in vitro against pathogenic fungi isolated from patients with dermatomycoses, and these findings emphasized the utility of luliconazole for the topical management of this condition.
Journal of Infection and Chemotherapy 07/2006; 12(3):163-5. · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine drug susceptibility of Trichophyton tonsurans endemic in Japan, in vitro MICs of antifungal drugs against a total of 10 clinical isolates of T. tonsurans collected from dermatophytosis patients were measured by the agar dilution method and the broth microdilution method. The agar dilution method was not appropriate as the growth of T. tonsurans on the agar medium was too slow to determine drug activity, while the broth microdilution method was thought to be an appropriate method for this study. The MIC90 values determined by the broth microdilution method for terbinafine, itraconazole, miconazole and ketoconazole were 0.013, 0.1, 0.8 and 0.4 microg/ml, respectively. Meanwhile, the MIC90 values of lanoconazole and luliconazole, known to be antifungal drugs potent against dermatomycosis, were 0.00078 and 0.00039 microg/ ml, respectively. The drug susceptibility of these T. tonsurans isolates to the aforementioned antifungal drugs was found to be on a similar level with that of T. mentagrophytes and T. rubrum, major causative agents of dermatomycosis. The results also demonstrated the strong antifungal activity of lanoconazole and luliconazole against T. tonsurans.