ISSN:0954-6634    

DOI:10.3109/09546639209088692

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Terbinafine (Lamisil®) is an orally active antimycotic of the allylamine class with activity against a wide range of pathogenic fungi, especially dermatophytes. The primary mechanism of action of these compounds is the specific inhibition of fungal squalene epoxidase. Measurement of ergosterol biosynthesis by incorporation of radiola-belled precursors indicates a correlation between inhibition of growth and of ergosterol biosynthesis in a range of pathogenic fungi. Fungi treated with these drugs accumulate squalene while becoming deficient in ergosterol, an essential component of fungal cell membranes. The characteristic primary fungicidal action of terbinafine and related allylamines is closely associated with the development of high intracellular squalene concentrations, which are thought to interfere with fungal membrane function and cell wall synthesis. Terbinafhe is a potent non-competitive inhibitor of the microsomal squalene epoxidase from Candida (Ki= 30 nM). In contrast, inhibition of rat liver squalene epoxidase only occurs at very high drug concentrations (Ki= 77μM) and is also qualitatively different, being competitive with squalene. Terbinafine thus has no effect on cholesterol biosynthesisin vivo. Squalene epoxidase is not an enzyme of the cytochrome P-450 type and, therefore, the allylamines have no intrinsic potential for inhibition of this class of enzymes.

ISSN:0954-6634    

DOI:10.3109/09546639209088693

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Terbinafine (Lamisil®) is a potent and specific inhibitor of fungal squalene epoxidase. Fungi treated with the drug accumulate large quantities of squalene in the form of lipid droplets but, due to its hydrophobicity, squalene partitions also into cellular membranes. Organelle membranes from terbinafine-treatedTrichophytoncells can contain up to 100 times more squalene than found in controls. In artificial phospholipid membranes, squalene destabilizes the bilaminar structure by inducing transition to the inverted micellar HIIphase. Thus, it can be assumed that high squalene concentrations produce disturbances in the structure of cellular membranes and thereby interfere with essential membrane functions. Biochemical and ultrastructural analyses ofTrichophyton mentagrophytestreated with terbinafine have provided evidence of perturbations of vital membrane-associated functions subsequent to squalene accumulation. Synthesis of membrane phospholipids was markedly reduced whereas the rate of degradation of the major membrane phospholipid, phosphatidylcholine, was increased. In cells treated with the drug, the appearance of the vacuoles was significantly altered and the biosynthesis of chitin drastically reduced.

ISSN:0954-6634    

DOI:10.3109/09546639209088694

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Information on the pharmacokinetics of terbinafine (Lamisil®) in the nail is essential for the rational planning of optimal therapeutic regimens. There are important inherent difficulties in delivering drugs in appropriate concentrations to diseased areas of the nail that are related to biochemical and physical properties of the nail plate. Whereas the inflammatory response and stratum corneum disruption in skin diseases may make it easier for drugs to reach their target, in disease of the nail plate, the crumbling and resultant lack of contiguity may add to the problems of drug penetration. Several clinical studies of terbinafine in onychomycosis have suggested that, because of its fungicidal properties, short courses of therapy can be effective. In a recent study in Cardiff, the levels of terbinafine in individual distal nail clippings were measured in 12 patients taking 250 mg of oral terbinafine daily for up to 48 weeks. Terbinafine was detected at a mean time of approximately 8 weeks, but as early as 3 weeks in one patient, confirming that terbinafine diffuses rapidly through nail. In another recent Cardiff study aimed at measuring the relationship of oral doses of terbinafine to both proximal and distal nail plate drug levels, and its persistence following cessation of therapy, the results appear to support the effectiveness of short-course terbinafine therapy. Nail pharmacokinetic data are still required to guide the optimal management of relapsers and slow responders, and nail drug levels as a clinical investigation may prove helpful in the management of some patients.

ISSN:0954-6634    

DOI:10.3109/09546639209088695

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Griseofulvin has been the standard therapy for dermatophyte onychomycosis, but is relatively unsuccessful, effecting a cure in only 30–40% of patients after 18 months. Of the new drugs for this indication, terbinafine (Lamisi®) appears to be the most successful. The first multicentre trial in the UK involved 103 patients receiving terbinafine at 250 mg/day for 12 and 6 months for toenail and fingernail infections, respectively; mycological cure rates were 80% and 95%, respectively. Mild gastrointestinal upset was the only reported adverse event. The relapse rate at 12 months after stopping therapy was 20%, but late cure was also seen, even in cases withScopulariopsisinfections. In a placebo-controlled trial of 12-week terbinafine treatment for nail infection at any site, mycological. cure rates were 82% and 71% for toenail and fingernail infections, respectively, in a total of 112 patients. Side-effects were again mainly gastrointestinal, but were more frequently reported with placebo. Clinical improvement was observed early in those successfully treated, allowing identification of those cases needing only 12 weeks of therapy for a good response. Terbinafine is safe and well tolerated in the treatment of dermatophyte onychomycosis, and is able to effect a cure in the majority of patients after only 12 weeks of treatment.

ISSN:0954-6634    

DOI:10.3109/09546639209088696

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Terbinafine (Lamisil®) is a new fungicidal agent of the allylamine class of drugs that is available as an oral or topical (1% cream) treatment. A study was designed to assess the efficacy of the topical formulation, in patients who had tinea cruris/corporis, compared with placebo when used once daily for only 1 week. Follow-ups were at 2 and 4 weeks after treatment. At the end of follow-up (4 weeks), 84% and 12.5% of terbinafine- and placebo-treated patients, respectively, were completely (mycolog-ically and clinically) cured. Furthermore, side-effects were rarely reported during the study.

ISSN:0954-6634    

DOI:10.3109/09546639209088697

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

An open clinical pilot study of terbinafine (Lamid®) in patients with tinea capitis had suggested that this agent was effective and well tolerated in the treatment of patients with this indication. On this basis, a double-blind randomized study comparing the efficacy and tolerability of terbinafine, given once daily for 4 weeks, and griseofulvin, given once daily for 8 weeks, was initiated. A 4-week placebo wash-out period separated the two active-treatment periods. Although this study is still in progress and the codes have not yet been broken, clinical and laboratory evaluation of 30 patients suggests that short-term (4-week) therapy with terbinafine is as effective and safe as 8 weeks of griseofulvin therapy in patients, including children, with tinea capitis.

ISSN:0954-6634    

DOI:10.3109/09546639209088698

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

The objective of this open parallel-group pilot study wa to assess the safety and efficacy of terbinafine (Lamisil®), a new allylamine antifungal agent, compared with griseofulvin in the treatment of tinea imbricata. The study was carried out in patients living in remote villages in the Central Kalimantan province of Indonesia. Patients entering the study had tinea imbricata due toTrichophyton concentricum, confirmed by mycological as well as clinical evaluation. A total of 55 patients were given either terbinafine at 250 mg once daily (n = 30) or griseofulvin at 500 mg once daily (n = 25) for 6 weeks, after which follow-ups were made at 2 and 5 months to assess relapse. Clinical and mycological examinations were carried out before and after treatment, and during follow-ups.All 30 patients taking terbinafine were evaluable and were completely (clinically and mycologically) cured (100%). In contrast, of the 23/25 evaluable patients taking griseofulvin, 16 (70%) were completely cured and 7 (30%) showed no response. After 2 months, follow-up showed that 2/30 (7%) in the terbinafine group and 5/16 (31%) in the griseofulvin group had relapsed. After 5 months, these relapse figures had increased to 7/27 (26%) and 5/15 (33%) in the terbinafine and griseofulvin groups respectively. Mild headache and sweating were the only side-effects reported in a smhll number of patients. No patients discontinued treatment nor were there changes in liver, kidney or haematological para-meters compared with pretreatment values. In conclusion, these results indicate that terbinafine is highly effective and well tolerated in patients with tinea imbricata.

ISSN:0954-6634    

DOI:10.3109/09546639209088699

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Terbinafine (Lamisil®), an allylamine antimycotic agent, has been shown to have excellent in-vitro activity against dermatophytes. Several other fungi of importance also show in-vitro sensitivity. Because terbinafiie is fungici-dal rather than fungistatic in action, its efficacy in treating such fungal infections requires evaluation. Five patients with cutaneous sporotrichosis were treated with 250 mg of terbinafine twice daily. All of the patients were cured. Overall, the clinical response was rapid. In three patients, negative culture was achieved within 8 weeks; in the other two, negative culture was obtained at 12 and 32 weeks, respectively. Terbinafine was well tolerated, although one patient developed erectile dysfunction while receiving treatment. This was completely resolved on stopping the treatment. The treatment of sporotrichosis is also reviewed in this article.

ISSN:0954-6634    

DOI:10.3109/09546639209088700

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

This study was designed as a double-blind, stratified, randomized parallel-group study to compare the efficacy and safety of terbinafine (Lamisil®), given for 12 weeks in a dose of 250 mg/day, and placebo in chronic candidal paronychia and candidal onychomycosis. Non-responders at the end of the 12-week treatment were allowed to receive a further 12 weeks of therapy. The results at 12 weeks showed no statistically significant difference in efficacy between terbinafine and placebo in the treatment of these conditions. A few patients were mycologically cured: three patients taking terbinafine remained negative whereas one taking placebo was positive again at the subsequent clinical visit. Some patients responded well to therapy, mainly those withCandida parapsilosisinfection. It is known that terbinafine is fungicidal against this species, but fungistatic againstCandida albicans. Where more than oneCandidaspecies was involved in the infection, and their distribution was more widespread with various species cultured from several sample sites, terbinafine was less effective. The overall tolerability of the drug was very good: No adverse events were reported nor changes noted on routine haematology and biochemistry screening.

ISSN:0954-6634    

DOI:10.3109/09546639209088701

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor