Terbinafine. An update of its use in superficial mycoses.

Terbinafine is an allylamine antifungal agent which has fungicidal activity against a wide variety of dermatophytes, moulds and certain dimorphic fungi, and fungistatic activity against Candida albicans. Oral terbinafine 250 mg/day is effective in the treatment of superficial dermatophyte infections such as onychomycosis, tinea pedis and tinea corporis/cruris, generally achieving mycological cure in > 80% of patients. The drug is also effective in children with tinea capitis when administered orally in the dosage range 62.5 to 250 mg/day for 4 weeks. Comparative data indicate that oral terbinafine is more effective than continuous or intermittent intraconazole in dermatophyte onychomycosis, and is as effective as itraconazole 400 mg/day in tinea pedis. The drug has shown greater efficacy than griseofulvin in dermatophyte onychomycosis, tinea pedis and tinea corporis/cruris, and comparable efficacy in children with tinea capitis. Additionally, oral terbinafine is more effective than ketoconazole 200 mg/day in tinea corporis/cruris. Topical terbinafine 1% formulations are effective when applied once or twice daily for up to 2 weeks, achieving mycological cure in > 80% of patients with tinea pedis, tinea corporis/cruris, cutaneous candidiasis and pityriasis versicolor. Its formulations are at least as effective as miconazole 2% cream and naftifine 1% gel in tinea pedis, and more effective than clotrimazole 1% cream, bifonazole 1% cream and oxiconazole 1% lotion. Mycological cure rates achieved with terbinafine generally improve after treatment cessation, reflecting the drug's fungicidal mechanism of action and its residual effect in tissue. Terbinafine is well tolerated after oral or topical administration and has a relatively low potential for drug interactions. Pharmacoeconomic data support the use of terbinafine in dermatophyte infections of the skin or nails. CONCLUSIONS: Evidence suggests that oral terbinafine is the treatment of choice for dermatophyte onychomycosis, as it achieves high rates of mycological and clinical cure, is generally well tolerated and has a relatively low potential for drug interactions. It must also be considered a first-line treatment option, along with itraconazole, in cutaneous mycoses which warrant systemic treatment; topical terbinafine is a treatment of choice in less extensive mycoses. The use of terbinafine in non-dermatophyte or mixed infections has not been fully defined.     

0.25%盐酸阿莫罗芬霜治疗体股癣和足癣随机单盲对照多中心临床试验

目的评价0.25%盐酸阿莫罗芬霜治疗体股癣和足癣的临床疗效及安全性。方法用随机单盲阳性药对照平行分组多中心临床试验,以1%联苯苄唑霜作对照,每天外用0.25%盐酸阿莫罗芬霜1次,疗程体股癣2周,足癣4周;停药后随访2周。结果在停药后2周,0.25%盐酸阿莫罗芬霜治疗体股癣和足癣的综合疗效、临床疗效、真菌学疗效和安全性评价与1%联苯苄唑霜比较均无显著性差异(P>0.05)。结论0.25%盐酸阿莫罗芬霜治疗体股癣和足癣安全、有效。     

复方硝酸益康唑软膏治疗体股癣及手足癣的临床疗效及安全性

目的：评价复方硝酸益康唑软膏治疗体股癣及手足癣疗效及安全性。方法：采用多中心、随机、双盲、平行对照法。135名体股癣及手足癣病人随机分为两组，分别用复方硝酸益康唑软膏和派瑞松软膏治疗。根据临床症状和体征，真菌镜检及／或培养结果进行疗效评价。结果：复方硝酸益康唑软膏的体股癣治愈率为53．49%，有效率为90．70％，手足癣治愈率为57.69％，有效率为96.15％，与对照组派瑞松相比,两者疗效相近，统计学无显著差异。结论：复方硝酸益康唑软膏是一种治疗体股癣及手足癣有效且安全的新型药物。     

1%盐酸布替萘芬软膏治疗体股癣和足癣随机双盲临床试验

目的评价1%盐酸布替萘芬软膏治疗体股癣和足癣的疗效和安全性,并与1%联苯苄唑霜比较。方法 每日外用1次,疗程为体股癣2周、足癣4周,随访2周。结果在停药后2周综合疗效显示,试验组治疗体股癣的痊愈率为81.0%,有效率为98.3%;对照组分别为70.5%和91.8%。试验组治疗足癣的痊愈率为47.6%,有效率为93.6%;对照组分别为50.8%和93.6%。2组间比较均无统计学差异(P>0.05)。结论1%盐酸布替萘芬软膏治疗体股癣和足癣疗效肯定,耐受性好,安全性高。     

伊曲康唑治疗浅部真菌病疗效观察

目的：了解国产伊曲康唑治疗浅部真菌病的疗效及安全性。方法：手足癣和体股癣患者，口服伊曲康唑200mg，为2次／d和1次／d连用7d，停药1周和3周评价疗效。结果：停药1周后手足癣和体股癣的痊愈率和显效率分别为75％和73．3％，总显效率为74．2％，真菌清除率为81．8％；3周后的痊愈率和显效率分别为88．9％和96．7％，总显效率为92．4％，真菌清除率为95．5％。结论：伊曲康唑是一种疗效高、安全性较好的抗真菌药物。     

特比萘芬治疗皮肤浅部真菌病80例

目的 :观察特比萘芬软膏对皮肤浅部真菌病的临床疗效和不良反应。方法 :皮肤浅部真菌病的病人 80例 (男性 51例 ,女性 2 9例 ,年龄 4 1a±s17a) ,全部病人真菌镜检阳性 ,并对其中 30例做真菌培养 ,给予国产特比萘芬软膏外用 ,每日 2次 ,体、股癣及花斑癣治疗 1wk ,手、足癣治疗 2wk。结果 :停药后 2wk临床有效率 :体癣 10 0 % ,股癣 10 0 % ,手癣 10 0 % ,足癣 86 % ,花斑癣 10 0 % ,临床总有效率为 99%。真菌清除率 :体癣 94 % ,股癣 95% ,手癣 10 0 % ,足癣 86 % ,花斑癣 90 % ,总清除率为 94%。全部病例未见明显不良反应。结论 :国产特比萘芬软膏治疗皮肤部真菌病疗效佳 ,不良反应少。     

新型外用抗真菌药卢立康唑

足癣、股癣和体癣的发病率较高,又极易复发,严重影响到患者的生活质量。2013年11月,美国FDA批准1%卢立康唑乳膏上市,外用治疗趾间足癣、股癣和体癣。该药是一种新型咪唑类外用抗真菌药,具有抗菌谱广、抑菌作用强的特点。研究显示1%卢立康唑乳膏外用治疗足癣、股癣和体癣安全有效,尤其是治疗股癣和体癣时,仅需每日1次,治疗1周,与目前其他治疗药物(需要治疗2周)相比,疗程更短。     

硝酸舍他康唑霜与咪康唑霜治疗足癣、体股癣的多中心随机双盲对照临床研究

目的评价2％硝酸舍他康唑霜治疗足癣和体股癣的疗效及安全性,并与2％咪康唑霜对照。方法用多中心随机双盲对照试验。试验组及对照组分别外用2％硝酸舍他康唑霜及2％咪康唑霜,每天2次,疗程4周。在治疗开始及治疗2,4,6周时进行观察。结果 足癣试验组66例,对照组61例;体股癣试验组62例,对照组64例完成了观察。足癣:试验组治疗4周时,临床有效率90.9％(对照组91.8％),真菌学清除率89.2％(对照组91.8％)。6周时,分别为100％(对照组98.4％)和95.5％(对照组93.4％)。总有效率93.9％(对照组90.2％)。体股癣:试验组治疗4周时,临床有效率96.8％(对照组100％),真菌学清除率100％(对照组98.4％)。6周时,分别为98.4％(对照组98.4％)和100％(对照组98.4％)。总有效率98.4％(对照组96.9％)。试验组药物不良反应发生率3.1％(对照组2.4％),表现为局部轻度刺激。结论2％硝酸舍他康唑霜治疗足癣和体股癣均安全有效。     

1％盐酸布替萘芬乳膏治疗浅部真菌病疗效观察

目的观察和评价1％盐酸布替萘芬乳膏治疗浅部真菌感染疗效和安全性。方法门诊随机抽样,选择体股癣、手足癣患者,共236例,男164例、女72例,排除非观察对象,分为治疗组、对照组,平行对照。2组在性别、年龄、病程及感染严重程度上差异无显著性,具有可比性。治疗组使用1％盐酸布替萘芬乳膏,对照组使用2％酮康唑乳膏。将药物均匀涂于患处,1次·d^-1。体股癣疗程2周,每周复诊1次;手足癣疗程4周,每2周复诊1次。所有患者停药2周后复诊1次,观察记录皮损改善程度,计算疗效指数,观察不良反应。结果体股癣经过2周治疗,治疗组完成观察治疗57例,有效率94．74％,对照组完成治疗48例,有效率91．67％;手足癣经过4周治疗,治疗组完成观察治疗46例,有效率93．48％,对照组完成观察治疗36例,有效率88．89％。2组不良反应轻微,其发生率：治疗组为3．89％、对照组为3．66％。结论1％盐酸布替萘芬乳膏是一种疗效好、安全性高、使用方便的治疗体股癣、手足癣的抗真菌药物。     

Terbinafine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in superficial mycoses.

Terbinafine is an orally and topically active allylamine antifungal agent with a primarily fungicidal action in vitro. Its spectrum of in vitro activity includes a broad range of dermatophyte, filamentous, dimorphic and dematiaceous fungi, and some yeast species. In clinical trials, mycological and overall efficacy rates of around 90 and 80%, respectively, have been achieved in cutaneous dermatophyte infections (tinea corporis/cruris and tinea pedis) with terbinafine, administered either orally (250 or 500 mg/day) or topically (a 1% cream applied twice daily). Similar rates of cure have been obtained with oral terbinafine in dermatophyte nail infections after relatively short treatment periods ranging from 3 to 12 months. Topical terbinafine has been effective in approximately 80% of patients with cutaneous candidiasis or pityriasis versicolor. Few comparative data have been published, but generally oral terbinafine appeared to be at least as effective as oral griseofulvin or ketoconazole in tinea corporis/cruris and more effective than griseofulvin in tinea pedis. Both oral and topical terbinafine have been very well tolerated in clinical trials to date, with only minor adverse effects reported. Although further research is required to establish the efficacy of terbinafine in comparison with other available therapies, as well as to fully clarify its tolerability profile, the early results obtained with terbinafine in superficial fungal infections are very encouraging. Terbinafine appears likely to become a first-line therapy for dermatophyte infections, particularly those affecting the nails.     

Bifonazole in the treatment of fungal skin infections in the tropics: a clinical and mycological study

Summary

A study was carried out in 40 patients with various superficial fungal diseases, confirmed by culture or microscopic examination, to assess the therapeutic efficacy and local tolerability of 1% bifonazole cream. Patients with more than one clinical diagnosis at the time of entry were treated according to the number of conditions present. The cream was applied once daily to the affected areas and treatment duration varied according to persistence or resolution of the clinical signs and symptoms in the individual patient. The results were evaluated by clinical and mycological examination 3 and 14 days after the end of treatment. A cure rate of 100% was achieved in cases of pityriasis versicolor, tinea corporis and candidiasis, and 90% in patients with tinea pedis. Clinical signs and symptoms disappeared completely in all but a few patients. No side-reactions were observed in any patient, and patch tests carried out in selected patients with known allergy and those with normal skin showed no evidence of any allergic or photosensitivity reaction to bifonazole.     

Bifonazole in the treatment of fungal skin infections in the tropics: a clinical and mycological study

A study was carried out in 40 patients with various superficial fungal diseases, confirmed by culture or microscopic examination, to assess the therapeutic efficacy and local tolerability of 1% bifonazole cream. Patients with more than one clinical diagnosis at the time of entry were treated according to the number of conditions present. The cream was applied once daily to the affected areas and treatment duration varied according to persistence or resolution of the clinical signs and symptoms in the individual patient. The results were evaluated by clinical and mycological examination 3 and 14 days after the end of treatment. A cure rate of 100% was achieved in cases of pityriasis versicolor, tinea corporis and candidiasis, and 90% in patients with tinea pedis. Clinical signs and symptoms disappeared completely in all but a few patients. No side-reactions were observed in any patient, and patch tests carried out in selected patients with known allergy and those with normal skin showed no evidence of any allergic or photosensitivity reaction to bifonazole.     

Antifungal activity of the new agent latoconazole in two tinea models.

In vitro and in vivo antifungal activities of the new imidazole derivative latoconazole ((+-)-(E)-[4-(2-chlorophenyl)-1,3-dithiolan-2-ylidene]-1- imidazolylacetonitrile, NND-318; CAS 101530-10-3) were studied in comparison with three major topical agents, clotrimazole, bifonazole and tolnaftate. The in vitro activity of latoconazole against dermatophytes was much stronger than that of any reference agent tested. Both the recently developed tinea pedis model and the conventional tinea model in guinea pigs were employed for evaluation of topical usefulness of latoconazole. The 1% solution or cream preparation of latoconazole was highly effective in both of the two tinea models and its 5 or more doses achieved almost complete mycological cure. However, both tinea models, especially the former, were considerably resistant to the therapeutic treatment of all of the reference drugs. These results suggest that latoconazole is a promising topical antifungal agent, probably applicable to the treatment of tinea pedis as well as other types of dermatomycoses.     

Therapeutic efficacy of a topical tolnaftate preparation in guinea pig model of tinea pedis

The therapeutic efficacy of a topical antifungal ointment containing 2% tolnaftate was studied in a guinea pig model of tinea pedis using the following four topical antifungal preparations commercially available as reference drugs: variotin (3,000 U/g ointment); phenyl-11-iodo-10-undecynoate (0.5% ointment); siccanin (1% ointment); and clotrimazole (1% cream). After the infection fully developed, the infected animals were treated twice daily with the testing drug or reference drug for consecutive four weeks. Therapeutic efficacy was mainly evaluated on the basis of the extent of the yield of fungal cultures from the infected skin tissues (infection intensity) at the end of the treatment period. In animal groups treated with tolnaftate as well as with three reference drugs, siccanin, phenyl-11-iodo-10-undecynoate and clotrimazole, the average infection intensity was significantly lower than that for untreated control group (P < 0.05-0.005) although no culture-negative animal was seen in any treated animal group. Comparing with all the reference drugs, tolnaftate was the most highly effective and there was significant difference in the average infection intensity between a tolnaftate treated and each reference drug-treated groups (P < 0.01-0.005). These results confirm the clinical usefulness of the current tolnaftate preparation in the treatment of patients with tinea pedis and probably other clinical forms of dermatophytoses.     

Fungicidal activity plus reservoir effect allow short treatment courses with terbinafine in tinea pedis

Terbinafine, a synthetic allylamine, exerts fungicidal activity against dermatophytes, the causative pathogens of tinea pedis. As proven in numerous clinical trials, tinea pedis can be effectively and safely treated by topical terbinafine. In fact, a 1-week application of terbinafine 1% cream eradicated fungal pathogens at least as effectively as 4-week treatment courses with topical azole derivative antifungals and showed lower relapse rates. A new innovative single-application formulation of terbinafine 1% in a film-forming solution produces a high concentration gradient on the skin surface and enables a prolonged (up to 13 days) exposure of the skin to terbinafine. High drug penetration into the skin results in an otherwise not obtained drug reservoir in the horny layer, the location of dermatophytes in tinea pedis. Although azole antimycotics can also effectively penetrate into the horny layer of the skin, short-term therapy might not be feasible due to its primarily fungistatic activity against dermatophytes. Thus, we conclude that the high efficacy of short-term treatment with terbinafine in patients with tinea pedis is possible due to its fungicidal activity coupled with a distinct reservoir formation in the upper layers of the epidermis.     

Ketoconazole: therapeutic results obtained in the district of Cagliari

The therapeutic results of ketoconazole treatment in 61 patients affected by mycoses at various locations are reported. The mycotic conditions in these patients were: pityriasis versicolor (26), tinea cruris (14), tinea corporis (8), tinea pedis (6), kerion celsi (6) and monilial granuloma (1). Clinical and mycological cure was obtained in 56 cases (91.8%) over a mean treatment period from a minimum of 29 days (pityriasis versicolor) to a maximum of 39 days (tinea pedis) and 150 days (monilial granuloma), with a mean daily dosage of 200 mg in adults and 100 mg in children. The authors stress the high level of tolerability of the drug and its high therapeutic activity. They indicate the conditions for its use in superficial epidermomycoses and kerion celsi and note its unparalleled effect in chronic mucocutaneous candidosis.     

特比萘芬软膏治疗浅部真菌病临床试验

目的 :评价特比萘芬软膏治疗浅部真菌病的疗效和安全性。方法 :2 0 2例浅部真菌病病人 (男性 12 7例 ,女性 75例 ;年龄 36a±s 12a)用特比萘芬软膏均匀涂布患处bid。体、股癣 ,花斑癣治疗 1wk ;鳞屑水疱型手、足癣治疗 2wk ;鳞屑角化型手、足癣治疗 4wk。结果 :总有效率为 91.1% ,真菌清除率 95.5%。不良反应发生率 2 %。结论 :特比萘芬软膏治疗浅部真菌病疗效显著且安全。     

Therapeutic efficacy of a topical antifungal solution preparation formulated with pyrrolnitrin and clotrimazole in combination (Pyroace W) in guinea pig model of tinea pedis

The therapeutic efficacy of a topical antifungal solution containing a mixture of 0.2% pyrrolnitrin and 0.4% clotrimazole (Pyroace W) was tested in a guinea pig model of tinea pedis using a 1% newly solution formulated preparation of miconazole (Dermalin-L) as a reference drug. Infected animals were treated once or twice daily with the testing drug and once daily with the reference drug for 4 weeks. Therapeutic efficacy was evaluated on the basis of the extent of the yield of fungal cultures from the infected skin tissues (infection intensity) and the relative number of culture-negative animals at the end of the treatment period. In an animal group treated once daily with the testing drug, the infection intensity was significantly lower than that for untreated or vehicle-treated control group (p < 0.0001) although there was no culture-negative animal. A similar extent of therapeutic efficacy was obtained with a once daily treatment with the reference drug, yielding one of ten culture-negative animal. A better efficacy was seen in animals treated twice daily with the testing drug; the infection intensity was further decreased to a significant level and eight of ten animals became culture-negative. These results demonstrated that twice daily treatment with the testing drug was highly effective in guinea pig model of tinea pedis, 80% of infected animals being mycologically cured. It confirms the clinical usefulness of this regimen in the treatment of patients with tinea pedis or other types of dermatophytosis.     

特比萘芬软膏与咪康唑软膏治疗浅部真菌病的比较

目的 :比较特比萘芬软膏和咪康唑软膏治疗浅部真菌病的疗效。方法 :特比萘芬组 80例 (男性 4 2例 ,女性 38例 ;年龄 4 2a±s 2 1a)手、足癣病人 4 0例 ,疗程 2wk ;体、股癣病人 4 0例 ,疗程 1wk。咪康唑组 6 0例 (男性 2 9例 ,女性 31例 ;年龄 4 2a±19a)手、足癣病人 30例 ,疗程 4wk ;体、股癣病人30例 ,疗程 2wk ,2组均每日 2次分别外用特比萘芬软膏和咪康唑软膏。结果 :特比萘芬组有效率停药时为 84 % (6 7/ 80 ) ,停药 2wk后为 92 % (74 / 80 ) ;咪康唑组停药时为 58% (35/ 6 0 ) ,停药 2wk后为53% (32 / 6 0 ) ,2组差异有显著意义 (P <0 .0 5)。真菌清除率停药 2wk后特比萘芬组为 94 % (35/ 80 ) ,咪康唑组为 6 8% (4 1/ 6 0 ) ,2组差异有非常显著意义(P <0 .0 1)。结论 :特比萘芬软膏治疗浅部真菌病较咪康唑软膏疗程短、疗效好     

复方硝酸益康唑乳膏的研制及疗效和安全性评价

目的制备复方硝酸益康唑乳膏,对质量控制方法进行研究,并进行临床研究。方法通过选择不同的乳化剂,进行处方筛选。采用高效液相色谱法测定含量。并对135例皮肤真菌病患者,采用多中心随机对照平行双盲法进行临床研究。结果通过选择不同的乳化剂,确定了最佳处方。建立了测定复方硝酸益康唑乳膏含量的方法,硝酸益康唑和醋酸曲安奈德的平均回收率分别为99.56%和99.49%(n=9),线性关系良好。复方硝酸益康唑乳膏对体股癣及花斑癣的治愈率为53.49%,有效率为90.70%,真菌转阴率为96.97%;对手足癣的治愈率为57.69%,有效率为96.15%,真菌转阴率为100%。结论处方设计合理。测定方法灵敏度高,专属性好,适用于复方硝酸益康唑乳膏的含量测定。临床疗效及安全性与对照药曲安奈德益康唑乳膏(商品名:派瑞松)相似。