ISSN:0954-6634    

DOI:10.3109/09546639009089020

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The primary fungicidal activity of the allylamines naftifine (Exoderil) and terbinafine (Lamid) shown in vitro for several strains of dermatophytic, filamentous and dimorphic fungi can be demonstrated in vivo in model systems for dermatophytoses. This quality of activity is accompanied by a rapid onset of action and leads to a superior antifungal efficacy when compared with fungistatic antimycotics.

ISSN:0954-6634    

DOI:10.3109/09546639009089021

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

ISSN:0954-6634    

DOI:10.3109/09546639009089022

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Two antimycotic agents, the azole ketoconazole and the allylamine terbinafine (Lamisil), have been examined for their effects on the metabolism of tolbutamide, ethinyloestradiol and cyclosporin by human liver microsomes (n = 4) in vitro. Ketoconazole caused marked inhibition of all enzyme activities with mean IC50values (concentration producing 50% inhibition) of 17.9μM (tolbutamide hydroxylase), 1.9μM (ethinyloestradiol 2–hydroxylase), 2.0μM (cyclosporineN-demethylase) and 2.1μM (cyclosporine hydroxylase). At 50μM terbinafine concentration, inhibition was less than 5% for tolbutamide, approximately 12% for both cyclosporin pathways and 30% for ethinyloestradiol. Terbinafine does not have the same inhibitory potential for cytochrome P-450 isozymes as ketoconazole.

ISSN:0954-6634    

DOI:10.3109/09546639009089023

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The pharmacokinetics of terbinafine (Lamisil) have been studied in humans using both unlabelled and radiolabelled drug. Lamisil is well absorbed (>70%) while maximal plasma concentrations of parent drug are reached within 2 hours following oral administration. Lamisil is extensively distributed to all tissues in the body with a total volume of distribution of approximately 1000 I (Vd). The half-life of elimination (β-phase) of Lamisil in man is approximately 16 hours. Lamisil is not excreted as an unchanged drug but is completely metabolized in the liver; 15 metabolites have been identified. Lamisil does not affect the metabolism of antipyrine, but its own metabolism is modified by the coadministration of either cimetidine or rifampicin.

ISSN:0954-6634    

DOI:10.3109/09546639009089024

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The percutaneous penetration of the antimycotic terbinafine (Lamisil, SF86–327) has been assessed after topical application in patients with pityriasis versicolor and normal volunteer subjects. Plasma samples were analysed by high-pressure liquid chromatography (HPLC). In 10 patients with pityriasis versicolor plasma levels over a 28–day period did not exceed 24.8 ng/ml. There was no evidence of long-term accumulation in these patients. Similar results were obtained with a group of 8 normal volunteer subjects where the maximum plasma level recorded after application of 1% terbinafine cream over 8 days was 11.4 ng/ml. Significantly higher values were not recorded in normal subjects with reduced barrier function. The two main metabolites of terbinafine, carboxybutyl and demethyl carboxybutyl terbinafine, were also measured by HPLC in the urine of the normal volunteer subjects. There was no evidence of long-term accumulation of the terbinafine or its metabolites in these subjects.

ISSN:0954-6634    

DOI:10.3109/09546639009089025

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The route of terbinafine (Lamisil) penetration into the stratum corneum after oral administration was studied in five patients. Serial skin surface biopsy samples of stratum corneum were taken after 1, 3, 7 and 14 days of treatment and terbinafine levels measured by high-performance liquid chromatography. Terbinafine was detected in the stratum corneum as early as 24 hours after the start of treatment in three of five patients. In all cases terbinafine was first detected in the deeper levels of stratum corneum, indicating that the route of delivery to stratum corneum after oral administration is initially by epidermal diffusion.

ISSN:0954-6634    

DOI:10.3109/09546639009089026

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

An antifungal drug with anti-inflammatory properties would offer the benefits of the available imidazole/steroid combinations without their disadvantages. Early in the development of the allylamine drug naftifine (Exoderil) routine toxicity studies demonstrated that it reduced inflammation in traumatized rabbit skin. This has been supported by further clinical and experimental investigations using various models of inflammation. Studies using an inflammatory response induced by sodium lauryl sulphate and UVB are in hand to verify these findings, and provide a guide as to the usefulness of the anti-inflammatory effect.

ISSN:0954-6634    

DOI:10.3109/09546639009089027

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Two examples of antifungal drugs belonging to the newly developed class of drugs referred to as allylamines have been evaluated for their efficacy, tolerability and pharmacokinetic profile when used topically in a 1% cream formulation for the treatment of dermatomycoses. These are naftifine (Exoderil) and terbinafine (Lamisil). Naftifine has been studied and is now used in a 1% gel as well, but this is not reviewed in this report. Both allylamines are very effective against a broad range of dermatophytes and yeasts causing tinea corporis, tinea cruris, tinea pedis, cutaneous candidiasis and pityriasis versicolor, and lead to mycological cure rates of 79–100% in the various indications. Both are well tolerated, rarely causing adverse events such as local irritation or burning at the site of application. Unique features of the drugs include their fungicidal action which has been shown by studies with terbinafine to allow short durations of treatment of 1–2 weeks and by studies with naftifine to be associated with anti-inflammatory activity. This new class of antifungal drugs appears to provide increased opportunity for successful treatment of dermatomycoses with topically applied formulations.

ISSN:0954-6634    

DOI:10.3109/09546639009089028

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Lamid is a new antifungal drug which can be administered orrally and is effective against a broad range of dermatomycoses. This report summarizes its mycological and clinical cure rates in 32 clinical studies in which it was used orally for the treatment of tinea corporis, tinea pedis (both interdigital and plantar types), onychomycosis of fingernails and toenails, cutaneous candidiasis and pityriasis versicolor. The pharmacokinetic profile shows Lamisil to be distributed extensively into lipophilic tissue and to have an elimination half-life from plasma which allows effective oncedaily administration. It diffuses from the vascular system into the stratum corneum where it binds, reaching levels well above the fungicidal concentrations against dermatophytes and yeast. In the treatment of over 1000 patients it has been shown to be very effective, leading to clinical cure in all the dermatomycoses listed above except pityriasis versicolor. It was particularly, and uniquely, effective in the most chronic forms of tinea pedis and onychomycosis. Lamisil is well tolerated, with only mild to moderate transient gastrointestinal side effects such as fullness, dyspepsia or nausea in a few patients. None of the hepatic or endocrine effects seen with imidazoles has been observed. Animal toxicology issues are reviewed. Lamisil meets a need for a new class of antifungal drug which is well tolerated, has rapid onset of action, can be used for short durations of therapy, is fungicidal and is active against chronic, resistant forms of dermatophyte infections of skin and nails.

ISSN:0954-6634    

DOI:10.3109/09546639009089029

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor