latoconazole and Tinea-Pedis

Hyperkeratotic type tinea pedis is a refractory type of superficial dermatomycosis. Treatment for hyperkeratotic type tinea pedis is mainly with oral antimycotics, such as griseofulvin, and healing is generally considered to be difficult with only topical antimycotics. In this randomized comparative study, the usefulness of a topical application of 1% lanoconazole cream (Astat) monotherapy (group I) was compared with that of combination therapy with 1% lanoconazole cream and 10% urea ointment (Pastaron) (group II) in a series of patients with hyperkeratotic type tinea pedis. The clinical improvement rates (percentage of 'marked improvement' plus 'moderate improvement') was 70.0% in group I and 95.7% in group II. The fungal eradication rate was 5.0% in group I and 43.5% in group II after 4 weeks of treatment, and was 70.0% and 95.7% after 12 weeks of treatment, respectively. The usefulness rate (percentage of 'very useful' plus 'useful') was 70% in group I and 95.7% in group II. Both lanoconazole monotherapy and the combination therapy with 10% urea ointment were highly effective and safe. Both treatments should be recommended for patients with hyperkeratotic type tinea pedis for whom an oral treatment is not appropriate or for whom a sufficient improvement with oral medications cannot be expected.

Topics: Administration, Topical; Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Drug Therapy, Combination; Female; Heterocyclic Compounds; Humans; Imidazoles; Keratosis; Male; Middle Aged; Ointments; Retrospective Studies; Time Factors; Tinea Pedis; Treatment Outcome; Urea

Lanoconazole (LCZ) is a topical antifungal agent clinically used to treat fungal infections such as tinea pedis. LCZ has not only antifungal effects but also anti-inflammatory effects, which have the potential to provide additional clinical benefits. However, the characteristic features of the inhibitory effects of LCZ on skin inflammation remain unclear.. We evaluated the inhibitory effects of topical application of LCZ, and compared the effects of LCZ with those of other antifungal agents including liranaftate, terbinafine and amorolfine.. Each antifungal agent was topically applied on 12-O-tetradecanoylphorbol-13-acetate-induced irritant dermatitis and 2,4,6-trinitrophenyl chloride-induced contact dermatitis in mice (BALB/c). The ear thickness, myeloperoxidase activity and inflammatory mediator contents were evaluated.. LCZ dose-dependently suppressed 12-O-tetradecanoylphorbol-13-acetate-induced irritant dermatitis, suppressed the production of neutrophil chemotactic factors such as keratinocyte-derived chemokine and macrophage inflammatory protein-2, and inhibited neutrophil infiltration to the inflammation site. Moreover, 1% LCZ reduced the ear swelling in mice with 2,4,6-trinitrophenyl chloride-induced contact dermatitis in accordance with the inhibition of interferon-γ production. The inhibitory potency of LCZ on these types of dermatitis in mice was stronger than that of other types of antifungal agents.. The anti-inflammatory effects of LCZ were exerted through the inhibition of inflammatory mediator production. These effects may contribute to the relief of dermatitis symptoms in patients with tinea pedis.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antifungal Agents; Dermatitis, Contact; Dose-Response Relationship, Drug; Ear, External; Female; Imidazoles; Mice; Mice, Inbred BALB C; Picrates; Tetradecanoylphorbol Acetate; Tinea Pedis

Dermatophytes are a group of keratinophilic fungi that invade and infect the keratinized tissues and cause dermatophytosis. We investigated effectiveness of novel triazole (luliconazole and lanaconazole) in comparison with available antifungal agents against dermatophyte species isolated from patients with tinea pedis.. A total of 60 dermatophytes species were isolated from the patients with tinea pedis. Identification of species was done by DNA sequencing of the ITS1-5.8S rDNA-ITS2 rDNA region. In vitro antifungal susceptibility testing with luliconazole and lanaconazole and available antifungal agent was done in accordance with the Clinical and Laboratory Standards Institute, M38-A2 document.. In all investigated isolates, luliconazole had the lowest minimum inhibitory concentration (MIC) (MIC range=0.0005-0.004μg/mL), while fluconazole (MIC range=0.4-64μg/mL) had the highest MICs. Geometric mean MIC was the lowest for luliconazole (0.0008μg/mL), followed by lanoconazole (0.003μg/mL), terbinafine (0.019μg/mL), itraconazole (0.085 μg/mL), ketoconazole (0.089μg/mL), econazole (0.097μg/mL), griseofulvin (0.351 μg/mL), voriconazole (0.583μg/mL) and fluconazole (11.58μg/mL).. The novel triazoles showed potent activity against dermatophytes and promising candidates for the treatment of tinea pedis caused by Trichophyton and Epidermophyton species. However, further studies are warranted to determine the clinical implications of these investigations.

Topics: Antifungal Agents; Arthrodermataceae; Dermatomycoses; Fluconazole; Griseofulvin; Humans; Imidazoles; Itraconazole; Ketoconazole; Microbial Sensitivity Tests; Terbinafine; Tinea; Tinea Pedis; Triazoles; Trichophyton; Voriconazole

Topics: Administration, Topical; Decanoic Acids; Dermatitis, Allergic Contact; Fatty Alcohols; Heterocyclic Compounds; Humans; Imidazoles; Male; Middle Aged; Ointments; Tinea Pedis

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

Two surface-active compounds, egg lecithin and polysorbate 80, usually used as the deactivators of various preservatives were tested whether they also counteract either or all of the three major topical antifungal drugs, bifonazole (BFZ), lanoconazole (LCZ) and terbinafine (TBF). Both egg lecithin and polysorbate 80, when added to culture media up to final concentrations of 1.0 and 0.7%, respectively, antagonized the anti-dermatophytic activity of the three drugs in a concentration-dependent manner. A greater extent of antagonistic action was exerted when the two deactivators combined at their maximal levels tested were added; MIC's of BFZ were increased more than 30-fold and those of LCZ and TBF more than 200-fold compared with the values obtained in the absence of the deactivators. Using the agar medium supplemented with the combined deactivators, culture studies were carried out with skin tissues specimens taken from guinea pigs whose feet were infected with dermatophytes and subsequently treated with 1% topical preparations of the three antifungal drugs. The experimental data from this animal study demonstrated that the combined deactivators-supplemented medium yielded increased numbers of fungi compared with the basal medium. It looks, therefore, likely that the fungal recovery on the former medium more correctly reflects to actual fungal burden in the infected lesions than the latter. All these results suggest that the combined deactivators-supplemented medium is more useful for mycological evaluation of therapeutic efficacy of imidazole and allylamine drugs against dermatophytoses in both preclinical and clinical studies.

Topics: Administration, Topical; Agar; Animals; Antifungal Agents; Culture Media; Disease Models, Animal; Female; Guinea Pigs; Heterocyclic Compounds; Imidazoles; Microbiological Techniques; Naphthalenes; Phosphatidylcholines; Polysorbates; Surface-Active Agents; Terbinafine; Tinea Pedis; Trichophyton

The therapeutic efficacy of short-term treatment with a 1% cream of lanoconazole, a new imidazole antimycotic agent, in comparison with that of a 1% cream of terbinafine was evaluated in the guinea pig model of tinea pedis. Each agent was topically applied once a day for 3 or 7 consecutive days, starting on day 10 postinfection, and a culture study was conducted on day 5 after the last treatment with each agent. The 1% cream of lanoconazole was as highly effective as the 1% cream of terbinafine in terms of eradicating the fungi from the infected feet.

Topics: Administration, Topical; Animals; Antifungal Agents; Guinea Pigs; Heterocyclic Compounds; Imidazoles; Male; Tinea Pedis

The therapeutic efficacy of ointment and cream preparations of lanoconazole in a guinea pig model of tinea pedis was compared. When infected animals were treated once daily with 0.25% and 0.5% lanoconazole ointments, 7 of 10 and 8 of 10 infected feet became culture-negative, respectively. In animals treated with 1% lanoconazole ointment, fungus was not recovered from any infected foot. Comparing these results with those of culture study in animals which were treated with comparable concentrations of lanoconazole cream, no significant differences were found. These studies, therefore, suggested that ointment and cream preparations of lanoconazole on topical application in the tinea pedis model would show basically equivalent therapeutic efficacy.

Topics: Administration, Topical; Animals; Disease Models, Animal; Guinea Pigs; Heterocyclic Compounds; Imidazoles; Male; Ointments; Tinea Pedis

Therapeutic efficacy of clinical dosage forms of latoconazole (NND-318, CAS 101530-10-3), related compound of ketene dithioacetals with an imidazole ring, was examined on two experimental tinea models: a recently developed tinea pedis model and a conventional tinea corporis model in guinea pigs. The efficacy of the dosage forms was estimated on the basis of the rate of fungus-positive skin cultures and/or the score of skin lesions, and was compared to the other antifungal agents, bifonazole, clotrimazole and tolnaftate. While these reference agents exhibited curative effect on the tinea corporis model, the tinea pedis model was considerably resistant to the therapeutic treatment of the agents. The cream preparation and solution of lactoconazole at concentrations of more than 0.25% were highly effective in either tinea models, and at concentrations of more than 1%, lactoconazole achieved complete mycological cure. These results suggest that 1% of lactonazole is an optimal concentration for clinical use.

Topics: Animals; Antifungal Agents; Guinea Pigs; Heterocyclic Compounds; Imidazoles; Male; Ointments; Tinea; Tinea Pedis

In vitro and in vivo antifungal activities of the new imidazole derivative latoconazole ((+-)-(E)-[4-(2-chlorophenyl)-1,3-dithiolan-2-ylidene]-1- imidazolylacetonitrile, NND-318; CAS 101530-10-3) were studied in comparison with three major topical agents, clotrimazole, bifonazole and tolnaftate. The in vitro activity of latoconazole against dermatophytes was much stronger than that of any reference agent tested. Both the recently developed tinea pedis model and the conventional tinea model in guinea pigs were employed for evaluation of topical usefulness of latoconazole. The 1% solution or cream preparation of latoconazole was highly effective in both of the two tinea models and its 5 or more doses achieved almost complete mycological cure. However, both tinea models, especially the former, were considerably resistant to the therapeutic treatment of all of the reference drugs. These results suggest that latoconazole is a promising topical antifungal agent, probably applicable to the treatment of tinea pedis as well as other types of dermatomycoses.

Topics: Animals; Antifungal Agents; Clotrimazole; Guinea Pigs; Heterocyclic Compounds; Imidazoles; Male; Microbial Sensitivity Tests; Tinea Pedis; Tolnaftate; Trichophyton