terbinafine, Lamisil
Lack of efficacy of 6-week treatment with oral terbinafine for tinea capitis due to Microsporum canis in children.

Dragos V, Lunder M.

University Medical Centre Ljubljana, Department of Dermatology, Slovenia.

Twenty-two children aged 2 to 9 years with noninflammatory tinea capitis due to Microsporum canis were evaluated in an open clinical pilot study run from January 1994 to July 1995. Each child was given oral terbinafine according to body weight for 6 weeks. Mycologic evaluation was done at the end of treatment and after follow-up periods of 4 and 8 weeks. None of the patients achieved complete mycologic cure by the end of the treatment period. Four weeks later complete mycologic cure was established in nine patients, and on final evaluation in seven. The treatment was very well tolerated by all the children. No systemic adverse effects were noted. According to our data, a 6-week course of oral terbinafine is inadequate for tinea capitis due to M. canis in children. Further study is needed to determine the most appropriate duration of therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9050765&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
Naturally azole-resistant Leishmania braziliensis promastigotes are rendered susceptible in the presence of terbinafine: comparative study with azole-susceptible Leishmania mexicana promastigotes.

Rangel H, Dagger F, Hernandez A, Liendo A, Urbina JA.

Laboratorio de Bioloia Celular de Parasitos, Facultad de Ciencias, Universidad Central de Venezuela, Caracas, Venezuela.

Leishmania braziliensis (isolate 2903) was naturally resistant to ketoconazole or the bis-triazole D0870, inhibitors of sterol C-14 demethylase, which produced only moderate effects on the proliferation of promastigotes at 10 microM. In contrast, Leishmania mexicana (isolate NR) was extremely susceptible to the azoles, as complete growth arrest and cell lysis were induced by incubation of the parasites with 0.05 microM concentrations of the drugs for 72 h. The opposite response was observed with terbinafine, an inhibitor of squalene epoxidase: L. braziliensis 2903 was three times more susceptible to the drug than L. mexicana NR (MICs of 5 and 15 microM, respectively). However, when the L. braziliensis stock was grown in the presence of 1 microM terbinafine, which by itself produced only marginal (< 10%) effects on growth, it became highly susceptible to the azoles, with an MIC of 0.03 microM. Analysis of cellular free sterols by high-resolution capillary gas chromatography coupled to mass spectrometry showed that 14-methyl sterols can support normal growth of L. braziliensis 2903 but not of L. mexicana NR. On the other hand, the higher susceptibility of the L. braziliensis isolate to terbinafine was correlated with a massive accumulation of squalene in the presence of the allylamine while no significant effects on L. mexicana sterol composition were observed at drug concentrations up to 1 microM. Thus, the > 300-fold increase in the susceptibility of L. braziliensis promastigotes to azoles in the presence of terbinafine was attributed to the combined effect of squalene and the methylated sterol precursors on the physical properties of the cell's membranes, leading to the loss of cell viability. Combination therapy with azoles and terbinafine in the treatment of human L. braziliensis infections deserves further study.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9124841&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
Differential inhibition of fungal amd mammalian squalene epoxidases by the benzylamine SDZ SBA 586 in comparison with the allylamine terbinafine.

Favre B, Ryder NS.

Department of General Dermatology NOVARTIS Research Institute, Vienna, Austria.

The allylamine class of antifungal compounds are specific inhibitors of squalene epoxidase (SE). However, depending on their chemical structure, allylamine derivatives can be highly selective for either fungal or mammalian SEs. All allylamines tested previously, irrespective of their selectivity, inhibit fungal SEs in a noncompetitive manner and mammalian SEs in a competitive manner. Here we have analyzed the inhibitory properties of the benzylamine SDZ SBA 586 toward fungal and mammalian SEs in comparison to the systemic antimycotic terbinafine, SDZ SBA 586 was, like terbinafine a selective inhibitor of fungal SE. Microsomal SE from the pathogenic yeast candida albicans was sixfold more sensitive to SDZ SBA 586 than to terbinafine, C50: 8 nM versus 44 nM, while the enzyme from the dermatophyte fungus Trichophyton rubrum was slightly less sensitive to SDZ SBA 586 than to terbinafine, IC50: 39 and 18 nM, respectively. Similarly to terbinafine, SDZ SBA 586 inhibited the yeast enzyme in non competitive manner, SDZ SBA 586 also inhibited mammalian microsomal SEs, but only at micromolar concentrations. It was more active than terbinafine toward both guinea pig SE, IC50: 2 microM versus 4 microM, and rat SE, IC50: 11 microM versus 87 microM. However, in contrast to terbinafine as well as allylamines selective for mammalian SE, SDZ SBA 586 was a noncompetitive inhibitor of rat microsomal SE. Interestingly, depending on the source of microsomal SE, binding of terbinafine and SDZ SBA 586 exhibited a positive, indifferent, or negative cooperativity, suggesting that SE is an oligomeric enzyme.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9143330&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
Effect of Lamisil and azole antifungals in experimental nail infection.

Richardson MD.

Department of Dermatology, University of Glasgow, UK. M.Richardson clinmed.gla.ac.uk

Onychomycosis is primarily caused by dermatophyte fungi but occasionally by yeasts and non-dermatophytic moulds. The aim of this study was to develop an in vitro model of nail invasion by dermatophytes, yeasts and non-dermatophytic moulds, and to provide an alternative system for studying the activity of different classes of antifungal drugs against fungi associated with onychomycosis. In the absence of extraneous nutrients, Trichophyton mentagrophytes was seen in electron microscopy to degrade completely healthy nail plate. Candida albicans germinated on nail fragments, but invasion of the nail plate was not seen. The mould Fusarium formed long channels through the matrix of the nail plate. Aspergillus versicolor appeared to penetrate the outer and intermediate surface of the nail plate only. Acremonium sp. and Scopulariopsis brevicaulis did not invade nail in this model. Exposure of nail fragments to terbinafine (0.25 mg/l for 3 h) inhibited invasion by T. mentagrophytes, C. albicans and the non-dermatophytic moulds. Itraconazole (0.25 mg/l for 3 h) prevented nail plate invasion by T. mentagrophytes, A. versicolor and Fusarium but did not totally inhibit the surface growth of Acremonium or S. brevicaulis. C. albicans grew in the presence of itraconazole. The results indicate that terbinafine is readily absorbed by the nail and that the drug is bio-available in nail keratin. A short exposure of nail to low concentrations of terbinafine acted as a barrier against fungal invasion. Itraconazole appeared to be effective against Trichophyton and some non-dermatophytic moulds.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9154398&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
Cloning and expression of squalene epoxidase from the pathogenic yeast Candida albicans.

Favre B, Ryder NS.

Sandoz Research Institute, Department of General Dermatology, Vienna, Austria.

The allylamine antimycotic terbinafine prevents the formation of sterols by specifically inhibiting squalene epoxidase (SE). The biological and biochemical action of terbinafine on fungal pathogens has been well investigated, but little is known at the molecular level. Here we report the cloning, sequencing and expression of the target of terbinafine from the major pathogen Candida albicans. A C. albicans genomic DNA library was constructed in gamma ZAP Express and screened with a DNA fragment obtained by polymerase chain reaction with two primers designed from sequences common to Saccharomyces cerevisiae and rodent SEs. Two types of clone, approximately 3.9 kbp and 4.1 kbp, were isolated. Both contained an identical open reading frame of 1488 nucleotides, while a few sequence differences were found in the flanking regions, suggesting an allelic heterogeneity. The deduced protein sequence of C. albicans SE, 496 amino acids (55324 Da), is 54% and 41% identical to those of S. cerevisiae and rat, respectively. A 1.8-kb transcript was observed on Northern blots of C. albicans mRNA. Polyclonal antibodies, raised against an internal peptide of C. albicans SE, recognized a protein associated with the particulate fraction of M(r) 55000 on Western blots of C. albicans extracts. C. albicans SE was overexpressed in S. cerevisiae with the expression vector pYES2. In homogenates from S. cerevisiae overexpressing the C. albicans protein SE activity was 10-fold higher than the endogenous activity from controls.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9161422&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
Open clinical study of the efficacy and safety of terbinafine cream 1% in children with tinea corporis and tinea cruris.

Bakos L, Brito AC, Castro LC, Gontijo B, Lowy G, Reis CM, Ribeiro AM, Souza FH, Villar Mdo L, Zaitz C.

Dermatology Service, Hospital das Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul Medical School, Brazil.

BACKGROUND: Topical application of antifungal agents is considered the treatment of choice for dermatomycoses. Most of the available drugs are fungistatic, requiring long term treatment to prevent relapses. Terbinafine is a synthetic antifungal agent that, because of its fungicidal action, provides high cure rates and low relapse rates after short periods of treatment. METHODS: Ninety-seven children ages 2 to 15 years with a suspected diagnosis of tinea corporis and/or tinea cruris were enrolled in this open trial. After mycologic assessment to confirm diagnosis (culture and direct microscopy) terbinafine 1% cream was applied once daily during 1 week. Clinical and mycologic assessments were made at the baseline visit and on Days 7, 14 and 21. Efficacy assessment was based on 88 children (9 patients excluded by protocol violation). RESULTS: Therapy was considered effective in 92.0% (81 of 88) of patients (complete clinical and mycologic cure or mycologic cure with minimum signs and symptoms or clinical improvement, > or = 50%). Tolerability was assessed in 97 patients on an intention-to-treat basis. Adverse reactions were itching 3% (3 of 97), itching associated with erythema exacerbation 1% (1 of 97) and contact dermatitis 1% (1 of 97). CONCLUSION: Terbinafine 1% cream appears to be an effective and well-tolerated treatment for tinea corporis and tinea cruris in children.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9194102&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
In vitro activities of terbinafine in combination with fluconazole and itraconazole against isolates of Candida albicans with reduced susceptibility to azoles.

Barchiesi F, Falconi Di Francesco L, Scalise G.

Institute of Infectious Diseases and Public Health of the University of Ancona, Italy. cmalinf popcsi.unian.it

A checkerboard microdilution method was applied to study the in vitro interaction of terbinafine with either fluconazole and itraconazole against 30 strains of Candida albicans. Synergy was observed in 40% of the terbinafine-fluconazole interactions and in 43% of the terbinafine-itraconazole interactions, while antagonism was not observed. Even when only additivity was achieved, the combinations still showed beneficial effects since at least twofold reductions in the MICs of both drugs were found in 100% of the terbinafine-fluconazole interactions and in 76% of the terbinafine-itraconazole interactions.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9257768&dopt=Abstract terbinafine Lamisil