ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1992.tb08394.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryTerbinafine (Lamisil®) has primary fungicidal action against many fungi as a result of its specific mechanism of squalene epoxidase inhibition. Treated fungi accumulate squalene while becoming deficient in ergosterol, an essential component of fungal cell membranes. The cidal action is closely associated with the development of high intracellular squalene concentrations, which are believed to interfere with fungal membrane function and cell wall synthesis. In the case ofCandida albicans,growth inhibition with terbinafine appears to result from the ergosterol deficiency. The filamentous form of this fungus is more susceptible than the yeast form. Measurement of ergosterol biosynthesis by incorporation of radiolabelled precursors indicates a correlation between inhibition of growth and ergosterol biosynthesis in a range of pathogenic fungi. Terbinafine is a potent non‐competitive inhibitor of squalene epoxidase fromCandida(Ki=30nm). In constrast, inhibition of rat liver squalene epoxidase only occurs at higher drug concentrations (Ki=77μm), and is competitive with squalene. Thus, terbinafine has no effect on cholesterol biosynthesisin vivo.Squalene epoxidase is not an enzyme of the cytochrome P‐450 type, thereby avoiding potential inhibition of this class of en

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1992.tb00001.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryThe dose‐dependency of the pharmacokinetic parameters of terbinafine and itsN‐demethyl derivative was investigated in a randomized four‐way crossover study in healthy volunteers following single oral administrations of 125, 250, 500 and 750 mg of terbinafine. Plasma concentrations of terbinafine and its metabolite were measured by a validated high‐performance liquid chromatography (HPLC) method using ultraviolet detection. Concentration data were fitted to a two‐compartment model. The relationship between Cmaxor the area under the concentration curve (AUC) and the terbinafine dose was analysed by classical linear regression. Terbinafine disposition parameters were dose‐independent, with the exception of Tmaxand t1/2x, which were prolonged with the 500‐ and 750‐mg doses. The terbinafine Cmaxand AUC, however, were linear and dose‐proportional over the entire dose range. TheN‐demethylated metabolite appeared in plasma at the same time as terbinafine and showed similar prolongations in Tmaxand t1/2xwith the 500‐ and 750‐mg doses. In addition, the Cmaxdeviated from proportionality at these doses, giving values 22% lower than projected, while the AUC was linear and dose‐proportional over the whole range of doses. The slight disproportionality in the dispositions of terbinafine and itsN‐demethyl metabolite at 500 and 750 mg are not expected t

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1992.tb00002.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryThe significance of contact allergy in patients with various oral symptoms was studied. Positive patchtest reactions to mercury compounds were found in 21/91 patients. Of these, 18 had lichenoid lesions in oral mucosa in close contact to amalgam fillings, and three patients with contact allergy had neither amalgam fillings in their teeth nor visible oral lesions. Amalgam replacement was carried out in 15/18 symptomatic patients. The fillings were replaced with gold in three cases, composite resin fillings in six, glass ionomer in three and both gold and composite materials in three cases. In 10 patients there was complete replacement and in five it was restricted to the fillings adjacent to the mucosal lesions. After a mean follow‐up period of 3.2 years a complete cure was seen in seven patients, each of whom had had all their fillings changed. A marked improvement occurred in six patients, and there was no change in tw

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1992.tb08395.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryFour antifungal drugs, the azoles ketoconazole, itraconazole and fluconazole, and the allylamine terbinafine, were studied for their effects on the metabolism of cyclosporine A (CyA) and cortisol by human liver microsomesin vitro(n=3). Ketoconazole produced marked inhibition of CyA hydroxylase (to metabolites M17 and M1) with IC50and Kivalues of 0.24±0.01 and 0.022±0.004μm, respectively. On the basis of the IC50, itraconazole was 10 times less potent (IC50of 2.2±0.2μm), and fluconazole and terbinafine were each above 100μm. No kinetic parameters were calculated for terbinafine because of the lack of inhibitory effects. Ketoconazole was the most potent inhibitor of cortisol metabolism (to 6β‐hydroxycortisol, IC50=0.6μm). Itraconazole produced marked inhibition of cortisol metabolism (IC50=2.4μm), but fluconazole and terbinafine had little effect. These data confirm that ketoconazole is a potent inhibitor of cytochrome P‐450‐IIIA4, and this has clinical relevance. Although the inhibition with fluconazole was much less than with itraconazole at equimolar concentrations, it should be noted that in‐vivo plasma concentrations of fluconazole are much greater than that of itraconazole. Clinical interactions of CyA with both fluconazole and intraconazole have been reported; in contrast to these azoles, terbinafine does not have the same inter

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1992.tb00003.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryIn a group of 612 consecutive patients undergoing routine patch tests for suspected allergic contact dermatitis, more than four‐fifths of the 364 women had had their ears pierced, over half gave a history of cutaneous reactions to metallic jewellery and almost one‐third were sensitive to nickel. The increase in the frequency of nickel sensitivity in women with pierced ears compared to those with unpierced ears was highly significant (P<0.001). In men, nickel sensitivity was much less frequent; occupational factors were often implicated and few cases were related to ear piercing. Jewellery dermatitis was more frequent in atopic than non‐atopic women but atopy did not appear to influence the propensity for developing nickel sensitivity in either sex. Ear piercing seems to induce nickel allergy which may result in lifelong morbidity and difficulty in employment. Jewellery suppliers should be encouraged to provide nickel‐free earrings to reduce the frequency of this apparently avoidable

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1992.tb08396.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryAntifungal drugs act by a variety of mechanisms. Agents such as substituent imidazoles and triazoles, which act by inhibiting the fungal cytochrome P‐450‐dependent enzyme lanosterolN‐demethylase, have the potential to inhibit host cytochrome pP‐450‐dependent drug metabolism. This is discussed with respect to ketoconazole, fluconazole and itraconazole. In contrast, allylamines, which have a different mode of action and a weaker ability to bind to cytochrome pP‐450, are not expected to inhibit clinical drug oxidation. Inducers of drug metabolism, especially rifampicin, phenobarbitone and phenytoin, may lower plasma (and tissue) concentrations of those antifungals metabolized by mixed function oxidases, with therapeutic c

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1992.tb00004.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryA computer omnibus survey to determine the prevalence of onychomycosis in the United Kingdom was carried out in the early part of 1990. A total population of 9322 adults, aged 16 years and over, was interviewed face‐to‐face, and a questionnaire completed, which consisted of questions and photographs of various nail dystrophies, including onychomycosis. The results in the population surveyed revealed a prevalence of dermatophyte nail infection of 2.8% in men and 2.6% in women. In the group aged 16–34 years, the prevalence rate was 1.3%; this increased to 2.4% in the group aged 35–50 years, and to 4.7% in those aged 55 years or over. Of those found to have onychomycosis, 27% had sought advice from a chiropodist and less than 12% had consulted a specialist. These results suggest that nearly 1.2 million people in the UK have a fungal nail infection and the majority had not sought medical advice, although over 80% stated that they would do so if they were aware that their nail disorder was of fungal origin. A similar proportion would wish to be treated if an effective treatment was av

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1992.tb00005.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryStandardized stereological methods were performed on biopsies from three subjects with normal skin and from three patients with autosomal dominant and three with autosomal recessive sex‐linked ichthyosis to determined the relative numbers and dimensions of desmosomes. The results showed an increase in the persistence of desmonsomes in the stratum corneum in both ichthyotic groups. This suggests a pathogenetic role for desmosomes in the abnormal desquamation of the two types of ichthyosis vulgari

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1992.tb08398.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryOral terbinafine is an effective therapy for dermatophyte onychomycosis, presumably because it reaches the infected areas of the nail rapidly and in fungicidal concentrations. For planning optimal clinical dosage regimes, it is necessary to know the rate of terbinafine movement through the nail plate, the concentrations achieved, and the persistence in the nail plate after stopping treatment. In a study of 12 patients receiving terbinafine at 250 mg/day for up to 48 weeks, measurement of terbinafine in distal nail clippings demonstrated that the drug was first detectable 3–18 weeks after starting therapy. A level of 0.25–0.55 ng/mg was quickly achieved and remained stable. Concentrations of terbinafine in distal clippings of unaffected nails were similar to those in affected nails. Although the average nail concentrations are within the fungicidal range for dermatophytes, the anatomy of an infected nail may result in relatively protected areas of infection. This results in the occasional persistence or recurrence of dermatophytic infection observed in some cases. However, the results of this study justify further trials of ‘short‐term’ oral terbinafine therapy for onychomycosis. A current study is addressing the relationship of oral dosage to nail drug concentration and its later persistence in the n

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1992.tb00006.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY