terbinafine, Lamisil
Euclidean and fractal computer-assisted corneofungimetry: a comparison of 2% ketoconazole and 1% terbinafine topical formulations.

Arrese JE, Fogouang L, Pierard-Franchimont C, Pierard GE.

Department of Dermatopathology, University of Liege, Belgium.

BACKGROUND: The corneofungimetry bioassay was designed as a unique model predicting the efficacy of topical and oral antifungals in dermatomycoses. OBJECTIVE: In this 2-step study performed in two groups of 15 volunteers, corneofungimetry was used to compare the effect of 5-day b.i.d. treatments with 2% ketoconazole and 1% terbinafine creams. METHODS: The bioassay was performed using 10 isolates of each of the 3 fungi Trichophyton rubrum, T. mentagrophytes var. interdigitale and Candida albicans put to grow on human stratum corneum. Controls were stratum corneum either untreated or enriched in propylene glycol contained in an unmedicated vehicle. Quantitative assessments were made using both Euclidean and fractal geometry parameters. RESULTS: In comparison with untreated stratum corneum, the fungitoxic activity of the 2% ketoconazole and 1% terbinafine formulations was obvious and similar against dermatophytes. By contrast, 2% ketoconazole was significantly more active against C. albicans than 1% terbinafine. The propylene-glycol-containing vehicle did not exhibit a significant effect upon the dermatophyte growth. Positive linear correlations were yielded between the extent area and the fractal dimension D of dermatophyte mycelia. By contrast, D appeared unrelated to the relative area of dermatophyte growth compared to controls. CONCLUSION: The combination of Euclidean and fractal analyses improves the information provided by the corneofungimetry bioassay. Creams containing 2% ketoconazole and 1% terbinafine appear equally effective against dermatophytes while the former is more potent against Candida albicans. Copyright 2002 S. Karger AG, Basel

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12037451&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
[Seven days of intermittent terbinafine 250 mg treatment in Tinea pedis]

[Article in Japanese]

Hamaguchi T, Takiuchi I.

Department of Dermatology, Showa University Northern Yokohama Hospital, Chigasaki chuo 35-1, Tsuzuki, Yokohama 224-8503, Japan.

Tinea pedis responds well to topical antifungal therapy, however, relapse of the disease is not uncommon. Long-term application of antifungals is usually necessary to control relapse. We conducted an open trial of a 7 day intermittent course of oral terbinafine treatment at 250 mg/day for plantar type and interdigital type of tinea pedis. Seventy-five patients of plantar type and 49 patients of interdigital tinea pedis were treated with a 7 day course of terbinafine 250 mg/day. Clinical assessments were made at baseline and every 4 weeks. Another 7 day course of the same amount of terbinafine were given depending on the clinical and the mycological response. Of the 75 plantar type tinea pedis with 8 patients excluded, 66 of the remaining 67 (98.5%) were evaluated as cured. Of the 49 interdigital tinea pedis (3 excluded), 43 of 46 patients (93.5%) cured. Relapse of the disease was observed in 4 of 51 patients at 1 year after treatment, 4 of 25 at 2 years, and 2 of 9 at 3 years in the plantar type, and in 4 of 30 at 1 year, 0 of 14 at 2 years, and 0 of 6 at 3 years in the interdigital tinea pedis group. Intermittent terbinafine therapy is thus effective in the treatment of tinea pedis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12040364&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
In vitro susceptibility of Microsporum canis and other dermatophyte isolates from veterinary infections during therapy with terbinafine or griseofulvin.

Hofbauer B, Leitner I, Ryder NS.

Infectious Diseases Department, Novartis Research Institute, Vienna, Austria.

We investigated the in vitro activity of terbinafine against fresh veterinary isolates of Microsporum canis and the potential of this organism to develop resistance in vivo during oral therapy. Dermatophyte cultures (n = 300) were obtained from naturally infected cats and dogs undergoing oral therapy with terbinafine or griseofulvin. M. canis comprised 92% of isolates; other species included Microsporum gypseum and Trichophyton mentagrophytes. Minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) of terbinafine and griseofulvin were determined by broth macrodilution assay. Terbinafine was highly active against all three species with MIC90< or =0.03 microg ml(-1), in agreement with published data. However, terbinafine exhibited primary cidal activity against 66% of Microsporum isolates (n = 275) in contrast to the almost complete cidal effect in Trichophyton (n = 18). Griseofulvin was significantly less active than terbinafine (MIC90 = 4 microg ml(-1)) but had a primary cidal action on about 40% of the isolates. The data were analysed for changes in MIC and MFC during the course of therapy, which could be indicative for development of acquired resistance. Oral treatment of 37 animals with terbinafine for up to 39 weeks caused no increase in MIC or MFC of terbinafine, either in individual patients or in the whole group.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12058731&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
Fungicidal activities of commonly used disinfectants and antifungal pharmaceutical spray preparations against clinical strains of Aspergillus and Candida species.

Gupta AK, Ahmad I, Summerbell RC.

Department of Medicine, Sunnybrook and Women's College Health Sciences Center, Toronto, Ontario, Canada. agupta execulink.com

The antifungal efficacy of commercial chemical disinfectants and pharmaceutical antifungal agents against medically important moulds and yeast species was investigated. Chlorine, phenol, sodium dodecyl sulfate and quaternary ammonium salts were the chemical disinfectants, and bifonazole and terbinafine were the antifungal pharmaceutical products tested against clinical isolates of Aspergillus and Candida species. Fungal inocula were obtained from conidial preparations of two A. ochraceus strains and yeast cells of C. albicans, C. krusei and C. parapsilosis. The antifungal activities were evaluated either by determining the kill rate in a cell suspension media at different contact periods, or by examining the viability and growth on plates sprayed with the active ingredient. Chlorine (1%) was the only disinfectant with the ability to cause a rapid inactivation of all five strains. Phenol (5%) was equally effective against Candida species; however, a number of A. ochraceus conidia were able to survive this treatment for up to 1 h. Benzalkonium chloride (0.5%) and cetrimide (0.5%) were also able to disinfect the three Candida species rapidly; however, these two quaternary ammonium compounds were relatively ineffective against A. ochraceus. In spray experiments, quaternary ammonium compounds had a fungicidal activity against Candida species and were fungistatic against A. ochraceus conidia. All five fungal strains were able to resist 0.5% sodium dodecyl sulfate, present either in the suspension solution or on the sprayed plate. Of the two pharmaceutical antifungal products tested, bifonazole (1%) were essentially ineffective against all five strains. Terbinafine (1%) had a fungicidal activity against A. ochraceus and C. parapsilosis. In suspension experiments, an exposure to 0.01% terbinafine required a contact period of 1 h for a complete inactivation of A. ochraceus conidia and an onset of fungicidal effect on C. parapsilosis yeast cells. Terbinafine was only moderately effective against C. albicans and was completely ineffective against C. krusei.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12058733&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
Physiologically based pharmacokinetic model for terbinafine in rats and humans.

Hosseini-Yeganeh M, McLachlan AJ.

Faculty of Pharmacy, University of Sydney, Sydney, New South Wales 2006, Australia.

The aim of this study was to develop a physiologically based pharmacokinetic (PB-PK) model capable of describing and predicting terbinafine concentrations in plasma and tissues in rats and humans. A PB-PK model consisting of 12 tissue and 2 blood compartments was developed using concentration-time data for tissues from rats (n = 33) after intravenous bolus administration of terbinafine (6 mg/kg of body weight). It was assumed that all tissues except skin and testis tissues were well-stirred compartments with perfusion rate limitations. The uptake of terbinafine into skin and testis tissues was described by a PB-PK model which incorporates a membrane permeability rate limitation. The concentration-time data for terbinafine in human plasma and tissues were predicted by use of a scaled-up PB-PK model, which took oral absorption into consideration. The predictions obtained from the global PB-PK model for the concentration-time profile of terbinafine in human plasma and tissues were in close agreement with the observed concentration data for rats. The scaled-up PB-PK model provided an excellent prediction of published terbinafine concentration-time data obtained after the administration of single and multiple oral doses in humans. The estimated volume of distribution at steady state (V(ss)) obtained from the PB-PK model agreed with the reported value of 11 liters/kg. The apparent volume of distribution of terbinafine in skin and adipose tissues accounted for 41 and 52%, respectively, of the V(ss) for humans, indicating that uptake into and redistribution from these tissues dominate the pharmacokinetic profile of terbinafine. The PB-PK model developed in this study was capable of accurately predicting the plasma and tissue terbinafine concentrations in both rats and humans and provides insight into the physiological factors that determine terbinafine disposition.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12069977&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
Inhibitory effect of terbinafine on reactive oxygen species (ROS) generation by Candida albicans.

Sander CS, Hipler UC, Wollina U, Elsner P.

Department of Dermatology and Allergology, Friedrich Schiller University, Jena, Germany. christina.sander derma.uni-jena.de

Candida albicans, the most important opportunistic fungal pathogen, is able to generate remarkable amounts of reactive oxygen species (ROS). Since ROS are highly cytotoxic, this mechanism may contribute to the pathogenicity of this yeast, including its invasiveness and the inflammatory response of the host. Terbinafine, a synthetic antifungal agent of the allylamine class, inhibits ergosterol biosynthesis at the level of squalene epoxidase. Furthermore, there is evidence that terbinafine at therapeutic concentrations can be considered a free radical scavenger in vitro and could exert an anti-inflammatory activity in vivo. In this study we investigated whether terbinafine affects the generation of ROS by C. albicans. Blastoconidia of the C. albicans strain 3153A were cultured in YEPG-medium and, subsequently, incubated with different doses of terbinafine (1, 10 and 100 microg ml(-1)) for 10 and 60 min, respectively. ROS generation was measured by lucigenin-enhanced chemiluminescence. Formation of ROS was considerably dependent on cell number. Chemiluminescence signals were measured at a concentration > or = 1 x 10(6) cells ml(-1), with a maximum of 1 x 10(8) cells ml(-)1. Already after 10 min of incubation with terbinafine, a dose-dependent significant inhibition of ROS generation was found (P < 0.05), whereas after 60 min this effect was amplified. In conclusion, terbinafine reduced the ability of C. albicans to generate ROS. Besides the known effect on ergosterol biosynthesis, this mechanism may contribute to its antifungal action.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12100530&dopt=Abstract terbinafine Lamisil