latoconazole and Disease-Models--Animal

Topical antifungal agents which have anti-inflammatory effects have the potential to provide additional clinical benefits. Therefore, an anti-inflammatory activity of lanoconazole (LCZ), a topical antifungal agent, was investigated against in vitro and in vivo models of inflammation. The release of interleukin-8 (IL-8) from human epidermal keratinocytes stimulated by the addition of 100 μg ml(-1) β-glucan of Saccharomyces cerevisiae was significantly inhibited by LCZ at the concentration of 10(-5) mol l(-1). The release of interferon-γ and IL-2 from human peripheral blood mononuclear cells stimulated by the addition of 30 and 100 μg ml(-1) phytohemagglutinin was significantly inhibited by LCZ at the concentrations of 10(-7) and 10(-6) mol l(-1), respectively. The increase in the ear thickness induced by topical application of 0.01% 12-O-tetradecanoyl phorbol-13-acetate and 1% 2,4,6-trinitrochlorobenzene (TNCB) after sensitisation with 3% TNCB were established as the mouse models of irritant and contact dermatitis, respectively. Application of 1% and 3% LCZ showed a significant anti-inflammatory activity against both the irritant and contact dermatitis models. These findings suggest that LCZ possesses an anti-inflammatory activity, which may be partially helpful in the treatment of dermatomycoses.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; beta-Glucans; Cells, Cultured; Dermatitis, Contact; Disease Models, Animal; Female; Humans; Imidazoles; Interferon-gamma; Interleukin-2; Interleukin-8; Keratinocytes; Leukocytes, Mononuclear; Mice; Phytohemagglutinins; Saccharomyces cerevisiae

The in vivo efficacy of terbinafine was compared to lanoconazole and luliconazole in the topical treatment of dermatophytosis caused by Trichophyton mentagrophytes using a guinea pig model. Topical antifungal treatment commenced three days post-infection, and each agent was applied once daily for seven consecutive days. Upon completion of the treatment period, evaluations of clinical and mycological efficacies were performed, as was scanning electron microscopy (SEM) analyses. Data showed that while all tested antifungals demonstrated significant mycological efficacy in terms of eradicating the fungi over untreated control, terbinafine and luliconazole showed superior clinical efficacy compared to lanoconazole (P-values < 0.001 & 0.003, respectively). Terbinafine demonstrated the highest clinical percent efficacy. SEM analysis revealed hairs from terbinafine and lanoconazole-treated animals had near complete clearance of fungi, while samples from luliconazole-treated animals were covered with debris and few conidia. This study demonstrates that, in general, terbinafine possessed similar efficacy to lanoconazole and luliconazole in the treatment of dermatophytosis. Terbinafine tended to have superior clinical efficacy compared to the azoles tested, although this difference was not statistically significant against luliconazole. This apparent superiority may be due to the fungicidal activity of terbinafine compared to the fungistatic effect of the other two drugs.

Topics: Administration, Topical; Animals; Antifungal Agents; Dermatomycoses; Disease Models, Animal; Guinea Pigs; Imidazoles; Male; Naphthalenes; Terbinafine; Treatment Outcome; 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 ointment and cream preparations of lanoconazole in a guinea pig model of tinea corporis was compared on the basis of degrees of improvement in local symptoms and negative culture rates. When infected animals were treated once daily with 0.25%, 0.5% and 1% lanoconazole ointments, significant improvement of the symptoms and mycological curative effects were observed as compared to those of non-treated control and vehicle-treated control groups of animals. Particularly, in animals treated with 0.5 or 1% lanoconazole ointment, no fungus was recovered from any infected loci. Comparing these results with those obtained with comparable concentrations of lanoconazole cream, no significant difference was found. These studies, therefore, suggested that ointment and cream preparations of lanoconazole on topical application would show basically equivalent therapeutic efficacy in the tinea corporis model.

Topics: Animals; Antifungal Agents; Disease Models, Animal; Guinea Pigs; Heterocyclic Compounds; Imidazoles; Male; Ointments; Tinea

The therapeutic efficacy of 1% cream and 1% solution of lanoconazole, a new imidazole antimycotic agent, in the model of cutaneous candidiasis in prednisolone-treated guinea pigs was evaluated in comparison with that of comparable formulations of bifonazole. Each preparation was topically applied once a day for 3 consecutive days, starting on the fifth day postinfection, and quantitative culture study wsa conducted on the ninth day postinfection. Both formulations of lanoconazole were much more highly effective in terms of eradication of fungi than the bifonazole formulations.

Topics: Administration, Topical; Animals; Antifungal Agents; Candida albicans; Candidiasis, Cutaneous; Disease Models, Animal; Drug Evaluation, Preclinical; Guinea Pigs; Heterocyclic Compounds; Imidazoles; Male; Microbial Sensitivity Tests; Prednisolone

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