terbinafine, Lamisil
Occurrence of dermatomycoses and in-vitro therapeutic efficacy of three antifungal drugs on the growth of Epidermophyton floccosum.

Awoderu VA, Nebo GC, Otudero VO.

Department of Biological Sciences, Olabisi Onabanjo University, P. M. B. 2002, Ago-Iwoye, Nigeria. awoderu ibadan.skannet.com.ng

The occurrence of dermatomycoses and the in-vitro therapeutic efficacy of some antifungal agents on dermatomycotic organisms were investigated. Of the 550 primary school children screened, the incidence was one hundred (18%), 70 were males (representing 20% of the males screened) and 30 females (15% of the females sampled). The differences between male and female prevalence were insignificant. Three species of dermatophytes were isolated and identified. These were Microsporum canis, Trichophyton tonsurans and Epidermophyton floccosum. The antifungal agents tested on E. floccosum were griseofulvin, terbinafine and ketoconazole. They produced different sized zones of inhibition against the growth of E. floccosum. Griseofulvin exhibited a 50% inhibition of growth on E. floccosum at 63.00 mg/L. Terbinafine on the other hand exhibited varying levels of inhibition of growth at varying concentrations, at 0.07 mg/L, terbinafine achieved 46% inhibition of growth on E. floccosum. The drug achieved 100% inhibition of growth on the isolate at 61.81 mg/L. In the case of ketoconazole, 50% inhibition of growth was achieved at 100 mg/L while 100% inhibition of growth was achieved at 200 mg/L. The antifungal effects of the three drugs were confirmed by broth dilution tests where terbinafine was found to be fungistatic on the growth of E. floccosum at concentrations ranging from 0.013-1.700 mg/L and was fungicidal at concentrations ranging from 0.027-1.700 mg/L. Ketoconazole was found to inhibit the growth of E. floccosum at 0.003-1.700 mg/L and was fungicidal at concentrations ranging from 0.027-1.700 mg/L. It however did not succeed in killing the isolate under the same range of concentrations. Griseofulvin exhibited fungistatic effects on the growth of E. floccusum at 0.013-1.700 mg/L. In conclusion, ketoconazole and griseofulvin were found to be fungistatic and not fungicidal while terbinafine was both fungistatic and fungicidal on the pathogen. Terbinafine was found to be the most effective drug in inhibiting E. floccosum.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14682454&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
Microbiological assay for terbinafine hydrochloride in tablets and creams.

Cardoso SG, Schapoval EE.

Departamento de Farmacia Industrial, CCS, Universidade Federal de Santa Maria, CEP 97119-900, RS, Santa Maria, Brazil. simonegc ccs.ufsm.br

The optimization of a microbiological assay, applying the cylinder-plate method, for the determination of the antifungal terbinafine hydrochloride is described. Using a strain of Aspergillus flavus ATCC 15546 as the test organism, terbinafine hydrochloride at concentrations ranging from 0.125 to 0.5 microg ml(-1) could be measured in tablets and creams. A prospective validation of the method showed that the method was linear (r=0. 9999), precise (intra-day: CV=0.48%-tablets and 0.43%-creams; inter-day: CV=0.98%-tablets and 0.64%-creams) and accurate (it measured the added quantities). The method shows results that confirm its precision, not differing significantly the others methods described in the literature. We conclude that the microbiological assay is satisfactory for quantitation of in vitro antifungal activity of terbinafine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10967433&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
Controlled release of terbinafine hydrochloride from pH sensitive poly(acrylamide/maleic acid) hydrogels.

Sen M, Uzun C, Guven O.

Department of Chemistry, Hacettepe University, 06532 Beytepe, Ankara, Turkey. msen eti.cc.hun.edu.tr

Adsorption and controlled release of terbinafine hydrochloride (TER-HCl) to and from pH sensitive poly(acrylamide/maleic acid) (P(AAm/MA)) hydrogels were investigated. P(AAm/MA) hydrogels were prepared by irradiating the ternary mixtures of AAm/MA/and water by gamma-rays at ambient temperature. Antifungal drug, TER-HCl containing hydrogels, at different drug to polymer ratios, was prepared by direct adsorption method. The influence of MA content in the gel on the adsorption capacities of hydrogel and the effect of pH on the releasing behavior of TER-HCl from gel matrix were investigated. Terbinafine adsorption capacity of hydrogels are found to increase from 2 to 38 mg TER-HCl per g dry gel with increasing amount of MA in the gel system. In vitro drug release studies in different buffer solutions show that the basic parameters affecting the drug release behavior of hydrogel are the pH of the solution and MA content of hydrogel.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10967437&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
Efficacy and tolerability of 8 weeks' treatment with terbinafine in children with tinea capitis caused by Microsporum canis: a comparison of three doses.

Devliotou-Panagiotidou D, Koussidou-Eremondi TH.

Department of Dermatology, Aristoteles University of Thessaloniki, Mycological Laboratory of the State Hospital for Skin and Venereal Diseases, Chalkidikis 51, GR-54644, Thessaloniki, Greece.

BACKGROUND: Tinea capitis caused by Microsporum canis is the most common mycosis of the scalp in preschool and school-aged children in Greece. OBJECTIVE: To compare the efficacy, safety and tolerability of an 8-week course of oral terbinafine at different doses. METHODS: Patients received oral terbinafine at doses ranging from 3.3 to 12.5 mg/kg/day for 8 weeks, as follows: group A, terbinafine 3.3 to </= 6.0 mg/kg/day (40 patients); group B, terbinafine > 6.0 to 7.0 mg/kg/day (23 patients); group C, terbinafine > 7.0 to 12.5 mg/kg/day (37 patients). Fungal microscopy and cultures were performed 4 weeks before the start of the treatment, at the end of the treatment (week 8) and at a follow-up visit at week 16. RESULTS: At week 8 mycological cure was achieved in one patient (2.7%) in group A, in 21 patients (91.3%) in group B and in 34 patients (97.1%) in group C. At week 16 mycological cure was achieved in one patient (2.7%) in group A, in 22 patients (95.7%) in group B and in 35 patients (100%) in group C. There was a statistically significant difference (P < 0.0005) between dose level and efficacy of terbinafine at the end of the treatment period and also at the follow-up visit at week 16. Five patients (three in group A and two in group C) discontinued treatment because of adverse events. CONCLUSIONS: The administration of terbinafine at a dose of either 6-7 or 7-12.5 mg/kg/day for 8 weeks is safe and effective for the treatment in children of tinea capitis caused by M. canis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15009293&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
Effect of infection with Trichophyton mentagrophytes varietas interdigitale on phagocytosis in humans.

Gregurek-Novak T.

Department of Dermatology, Clinical Hospital 'Sestre milosrdnice', Vinogradska 29, 10000 Zagreb, Croatia.

BACKGROUND AND AIM: Phagocytosis by polymorphonuclear leucocytes (PMNLs) and macrophages is important in the defence of human organisms, especially in mycotic infections of the skin. The aim of this study was to examine the relationship between phagocytosis and a chronic type of infection with Trichophyton mentagrophytes varietas interdigitale (T. m. var. interdig.). MATERIALS AND METHODS: A group of 256 patients was investigated from 1990 to 2000. They were all treated with terbinafine. The parameters for phagocytosis were analysed by the Hersy method. RESULTS: The immunological status of all of the patients was altered. Ingestion, digestion and random mobility decreased significantly (P < 0.001). Out of 256 patients treated with terbinafine, 196 (76%) were cured completely and the values for phagocytosis became normal. CONCLUSION: This investigation confirms the defect in the function of phagocytes of patients chronically infected by T. m. var. interdig. Terbinafine was shown to be an effective antimycotic drug, both fungicidal and immunostimulative.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15009294&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
In vitro activity of terbinafine against medically important non-dermatophyte species of filamentous fungi.

Garcia-Effron G, Gomez-Lopez A, Mellado E, Monzon A, Rodriguez-Tudela JL, Cuenca-Estrella M.

Servicio de Micologia, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Ctra Majadahonda-Pozuelo Km 2, 28220 Majadahonda, Madrid, Spain.

OBJECTIVES: The activity in vitro of terbinafine against 442 clinical isolates of several species of filamentous fungi was analysed. METHODS: A broth microdilution test was carried out following the National Committee for Clinical Laboratory Standards reference method, with modifications described previously. RESULTS: The geometric mean (GM) of MICs of terbinafine for non-Aspergillus fumigatus species was 0.24 mg/L whereas the GM for A. fumigatus rose as far as 2.92 mg/L. Terbinafine showed a very strong activity in vitro against Penicillium spp., Paecilomyces spp., Trichoderma spp., Acremonium spp. and Arthrographis spp. with GMs <1 mg/L. However, some species such as Scedosporium spp., Fusarium spp., Scopulariopsis brevicaulis, and most of Mucorales exhibited high MICs of the allylamine with GMs >/= 4 mg/L. CONCLUSIONS: Overall, the GM of MICs of terbinafine was 1.57 mg/L, but significant differences in susceptibilities were seen between genera and species.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15102749&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
Antifungal drug response in an in vitro model of dermatophyte nail infection.

Osborne CS, Leitner I, Favre B, Ryder NS.

Infectious Diseases Department, Novartis Research Institute, Vienna, Austria. colin.osborne pharma.novartis.com

Despite terbinafine being fungicidal against Trichophyton rubrum in standard NCCLS assays and rapidly accumulating in nails in vivo, onychomycosis patients require prolonged terbinafine treatment to be cured. To investigate this, we developed a more clinically relevant onychomycosis in vitro test model. Human nail powder inoculated with T. rubrum and incubated in liquid RPMI 1640 salt medium, which did not support growth alone, developed extensive and invasive mycelial growth. Antifungal drugs were added at different concentrations and cultures incubated for 1 to 4 weeks. Fungal survival was determined by spreading cultures on PDA plates without drug and measuring CFU after 1 to 4 weeks incubation. Drug activity was expressed as the nail minimum fungicidal concentration (Nail-MFC) required for 99.9% elimination of viable fungus. Terbinafine Nail-MFC was 4 microg/ml after 1 week exposure, decreasing to 1 microg/ml after 4 weeks exposure, much higher than MFCs < or = 0.03 microg/ml determined in standard NCCLS MIC assays. In contrast, other clinically used drugs were unable to kill T. rubrum after 4 weeks incubation in this model. Invasive mycelial growth on nail appears to protect T. rubrum from the cidal action of systemic drugs, thus providing a rationale for the long treatment periods in onychomycosis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15124869&dopt=Abstract terbinafine Lamisil