联苯苄唑乳膏体内外抗真菌活性及体内抗炎作用研究

目的 探讨1%联苯苄唑乳膏体内外抗真菌活性及体内抗炎作用。方法 采用豚鼠癣病模型、真菌体外药敏试验及小鼠二甲苯耳廓肿胀法评价1%联苯苄唑乳膏体内外抗真菌活性及体内抗炎作用。结果 1%联苯苄唑乳膏能有效治愈豚鼠须毛癣菌感染；体外抗皮肤癣菌和念珠菌最小抑菌浓度范围为 0.016 ～ 0.5 mg/L，最小杀菌浓度范围为0.063 ～ 2.0 mg/L；该药能显著抑制二甲苯所致的小鼠耳廓肿胀。结论 1%联苯苄唑乳膏具有明显抗皮肤癣菌、抗念珠菌和抗炎作用。     

O.25%盐酸阿莫洛芬霜治疗体股癣多中心的临床试验

目的评价0.25%盐酸阿莫罗芬霜治疗体股癣临床非劣效性及安全性.方法101例患者入选,采用随机单盲、阳性药(1%联苯苄唑霜)平行对照临床试验,根据临床症状改善及病原学检查、不良反应发生情况评价治愈率及安全性.结果试验组和对照组治愈率分别为80.0%、73.3%(P＞0.05,RR 1.09,C10.87-1.37);直接显微镜检查真菌阴转率分别为82.2%和73.3%(P＞0.05);真菌培养清除率分别为80.0%和73.3%(P＞0.05).个别患者发生与研究药物有关的不良反应,主要表现为红斑、瘙痒、灼热感、脱屑,不影响治疗,均自行缓解.ITT分析结果相似.结论0.25%盐酸阿莫罗芬霜治疗体股癣高效安全,且临床疗效、真菌学疗效和安全性均与1%联苯苄唑霜相似.     

Ultra-short topical treatment of pityriasis versicolor with 2.5% bifonazole cream

The therapeutic efficacy of a preparation containing 2.5% bifonazole was investigated by comparing three different treatment modalities—A, B, and C. Group A used bifonazole only on Day 1, Group B applied the cream on Days 1, 2 and 3, and the Group C on Days 1, 3 and 5. Of the patients in Group A 56% had a negative mycological examination at the end of the study. The results obtained in Groups B and C were not significantly different: 92% of the patients had a negative mycological examination at the end of the study. Electron microscope (EM) studies showed morphological alterations such as loss of cytoplasmic organization with shrinkage and folding of the cell membranes after 1 week of treatment only in Groups B and C. We conclude that 2.5% bifonazole is a highly effective treatment for Pityrosporum ovale infection when applied using a 3-day schedule.     

1%盐酸布替萘芬乳膏治疗浅部真菌病临床观察

目的：评价1％盐酸布替萘芬乳膏治疗浅部真菌病的临床疗效及安全性，并与1％联苯苄唑凝胶进行比较。方法：对83例浅部真菌病患者进行治疗，其中治疗组43例，外用1％盐酸布替萘芬乳膏，每日1次；对照组40例，外用1％联苯苄唑凝胶，每日1次，体股癣疗程2周，手足癣4周。分别于停药及停药2周时观察记录患者的临床表现及治疗效果。结果：1％盐酸布替萘芬乳膏和1％联苯苄唑凝胶临床疗效相似，停药时临床总有效率分别为90．7％和90．0％，真菌总清除率为93．0％和90．0％；停药2周时临床总有效率分别为97．7％和92．5％，真菌总清除率为100．0％和92．5％。不良反应少。结论：1％盐酸布替萘芬乳膏治疗浅部真菌病疗效显著且安全。     

Fenticonazole cream once daily in dermatomycosis, a double-blind controlled trial versus bifonazole

A randomized, double-blind clinical trial was undertaken in 41 patients with dermatomycosis to compare topical 2% fenticonazole cream (group A: 21 patients) with topical 1% bifonazole cream (group B: 20 patients). Treatment was performed as a once daily application. Mycological and clinical parameters were assessed before treatment and after 7, 14, 21 and 28 days. At the control visits the clinical investigator also expressed an overall judgement on the patient's state of disease. This parameter was based on a combined clinical and mycological assessment by the physician; laboratory screening investigations were undertaken before and at the end of treatments. All patients were checked for their state of disease 3-4 weeks after the end of treatment. All assessment criteria showed fenticonazole to be at least as efficacious as bifonazole. Several trends in favor of fenticonazole were also found: fenticonazole achieved superior results in the overall clinical evaluation, and after 3 weeks of treatment 15 patients out of 21 on fenticonazole were cured in mycological and clinical terms, whereas treatment with bifonazole resulted in complete healing of only 7 patients out of 20. This difference is statistically significant (p = 0.021) and indicates a more rapid therapeutic activity of fenticonazole. At the posttreatment rechecks no recurrent disease was registered, irrespective of whether patients had received fenticonazole or bifonazole. Laboratory screening investigations revealed no evidence of significant treatment-related changes or abnormalities in both treatments. No adverse events were noted for either treatment.     

Comparative study between terbinafine 1% emulsion-gel versus ketoconazole 2% cream in tinea cruris and tinea corporis

An open, prospective, comparative, randomised and parallel-group study of 65 patients was conducted to evaluate the efficacy and safety of topical 1 % emulsion-gel of terbinafine versus 2% ketoconazole cream in the treatment of tinea corporis and tinea cruris. Treatment for terbinafine emulsion-gel was applied once daily for 1 week, whereas ketoconazole cream was applied once daily for 2 weeks; patients were followed for 2 weeks. Thirty-three patients in the terbinafine group and 32 in the ketoconazole group were evaluated for efficacy and safety. At the end of the study, rates of mycological cure were 94% for terbinafine emulsion-gel and 69% for ketoconazole cream (p = 0.027). A clinical and mycological overall evaluation was obtained for 72% of patients receiving terbinafine emulsion gel and 31% of patients receiving ketoconazole cream (p = 0.002). A total of four patients (1 in the terbinafine group and 3 in the ketoconazole group) had contact dermatitis-like side effects. We conclude that a 1-week course of terbinafine 1% emulsion-gel is significantly more effective than ketoconazole 2% cream in the treatment of tinea corporis and tinea cruris as regards clinical and mycological cure and treatment safety.     

不同疗程1%卢立康唑乳膏治疗足癣的多中心、随机双盲对照研究

目的 观察和评价不同疗程1%卢立康唑乳膏治疗足癣的疗效和安全性。 方法 采用多中心、随机、双盲、阳性药物对照研究,将入选患者按照试验中心分层随机分成3组,包括卢立康唑短疗程组（外用1%卢立康唑乳膏,每日1次,共2周,后2周使用安慰剂）、卢立康唑长疗程组（外用1%卢立康唑乳膏,每日1次,共4周）、联苯苄唑对照组（外用1%联苯苄唑乳膏,每日1次,共4周）。开始用药后第2、3、4、6周评价临床和真菌学疗效。 结果 420例真菌镜检阳性的患者随机分成3组,每组140例,398例患者进入疗效分析。用药2周时,对照组、短疗程组、长疗程组临床有效率分别为29.29%、31.43%和35.00%（P > 0.05）,真菌清除率分别为49.29%、58.57%和57.86%（P > 0.05）;用药3周时,临床有效率分别为73.57%、78.57%和70.00%（P > 0.05）;用药4周时,临床有效率分别为89.29%、91.43%和89.29%（P > 0.05）,真菌清除率分别为80.00%、87.86%和85.00%（P > 0.05）。停药后2周,对照组、短疗程组、长疗程组的临床有效率分别是92.14%、92.86%和92.14%（P > 0.05）,真菌清除率分别为80.71%、90.00%和89.29%（P < 0.05）。对照组局部不良反应发生率为0.71%,短疗程组为0,长疗程组为2.14%。 结论 1%卢立康唑乳膏外用治疗足癣安全有效,每日1次治疗2周与治疗4周的疗效相当。     

1%联苯苄唑乳膏封包治疗甲真菌病49例分析

目的评价1%联苯苄唑乳膏封包治疗甲真菌病的临床疗效。方法回顾性分析2007年1月-2009年12月本科以1%联苯苄唑全程封包治疗甲真菌病患者的临床疗效。结果指甲真菌病依从性良好组和依从性不良组的有效率分别为86.67%和38.46%,趾甲真菌病依从性良好组和依从性不良组的有效率分别为82.76%和37.50%,差异均有统计学意义(P均<0.05)。且治疗过程中均无不良反应。结论 1%联苯苄唑乳膏全程封包治疗对甲真菌病疗效确切,安全性高,经济实惠。     

A randomized trial of amorolfine 5% solution nail lacquer in association with itraconazole pulse therapy compared with itraconazole alone in the treatment of Candida fingernail onychomycosis

BACKGROUND: Treatment failures and relapses are not uncommon in onychomycosis. Therefore, it is worthwhile to consider the combination of systemic and topical antifungals to improve the cure rates further and to reduce the duration of systemic treatment. OBJECTIVES: To evaluate and compare itraconazole pulse therapy combined with amorolfine with itraconazole alone in the treatment of Candida fingernail onychomycosis. METHODS: Ninety patients with moderate to severe Candida fingernail onychomycosis were randomized into two treatment groups of 45 subjects each. Group 1 received itraconazole pulse therapy for 2 months and applied amorolfine 5% solution nail lacquer for 6 months, while group 2 received monotherapy with three pulses of itraconazole. The primary efficacy criterion was the result of mycological examination at 3 months. The secondary criterion was the combined mycological and clinical response at 9 months. A pharmacoeconomic analysis was also performed to compare the cost-effectiveness of combined therapy vs. monotherapy. RESULTS: Eighty-five patients were analysed (73 women and 12 men, mean +/- SD age 44.2 +/- 12.9 years). Patients had a mean +/- SD of 3.64 +/- 2.0 nails involved and 228.6 +/- 148.0 mm2 of their nail surface diseased. The mean duration of onychomycosis was 11 months. Paronychial involvement was evident in 71 patients. C. albicans was isolated in 85 cases, C. parapsilosis in three and other Candida species in two cases. Side-effects were uncommon and in only one case led to withdrawal. At the 3-month visit, mycological cure was seen in 32 (74%) of 43 patients in group 1 and in 25 (60%) of 42 patients in group 2. At the 9-month visit, a global cure was seen in 40 patients (93%) in group 1 and in 34 patients (81%) in group 2. Statistical analysis showed no statistically significant difference (P > 0.1) between the two treatment groups. The cost per cure ratio was 1.63 and 1.70euro for groups 1 and 2, respectively. CONCLUSIONS: The combination of amorolfine and oral itraconazole, which interfere with different steps of ergosterol synthesis, exhibited substantial synergy. Compared with oral itraconazole alone, the combination achieved greater mycological cure and increased total cure rate. However, no statistically significant difference was documented for this number of observations. Combination treatment with amorolfine and two pulses of itraconazole is at least as safe and effective as three pulses of itraconazole, with a lower cost per patient. In our opinion, the addition of amorolfine to oral itraconazole pulse therapy is of value in the treatment of moderate to severe Candida fingernail onychomycosis.     

A pilot study of treatment of lentigo maligna with 5% imiquimod cream

BACKGROUND: Lentigo maligna (LM) is an in situ form of malignant melanoma, and surgical excision is often unsatisfactory. Imiquimod cream is an immune response modifier and induces a predominantly T-helper 1 type response. OBJECTIVES: Assessment of histological and clinical response of surgically resectable LM after treatment with 5% imiquimod cream. METHODS: Six patients with LM were treated with 5% imiquimod cream daily for 6 weeks. The whole site of the original lesion was then excised. Clinical and histological and appearances were measured using clinical response and histological grading scores. RESULTS: Complete or almost complete clearance of pigmentation with minimal residual histological evidence of LM was observed in four patients, one patient showed no clinical or histological improvement, and the remaining patient had almost no residual pigmentation clinically after treatment yet histopathological changes remained as severe as before treatment. CONCLUSIONS: Topical imiquimod cream merits further investigation as a new therapy for LM.     

Terbinafine 1% cream vs. bifonazole 1% cream in the treatment of tinea cruris

A total of 185 patients with a clinical diagnosis of tinea cruris and a positive mycologic examination were recruited into this double-blind randomized multicenter study comparing 1% terbinafine cream once daily for 1 week and 2 weeks placebo with 1% bifonazole cream applied once daily for 3 weeks. At the first visit and 1, 2, 3, and 8 weeks after the start of the study, signs and symptoms were assessed clinically and scores were taken for mycologic assessments (microscopy and culture). Assessments of clinical signs and symptoms were scored as follows. Pruritus: 0 = absent; 1 = mild, occasionally disturbing daily activities; 2 = severe, frequently disturbing daily activities and sleep. Erythema: 0 = absent; 1 = redness; 2 = bright redness, easily visualized. Scales: 0 = absent; 1 = scarcely visible and only in some areas; 2 = thick, covering a large area. Papule: 0 = absent; 1 = scarcely distributed; 2 = densely distributed and/or in the presence of plaques. At weeks 1, 2, 3, and 8, the effectiveness of therapy was clinically evaluated globally and given a rating of cured = 0, mild = <4, or severe = 4–8. The primary efficacy parameter was the mycologic cure rate at the follow-up weeks during treatment and 5 weeks after the end of treatment. The tolerability of the study medication was assessed at weeks 1, 2, and 3 of follow-up. Adverse events were also recorded at the same time. Routine hematologic and biochemical tests were performed at the start of the study and at the end of treatment.     

Comparison of mometasone furoate 0.1% cream and hydrocortisone 1.0% cream in the treatment of childhood atopic dermatitis

We conducted a 6-week randomized, blinded study that compared mometasone furoate 0.1% cream, applied once daily, and hydrocortisone 1.0% cream, applied twice daily, in 48 children with moderate to severe atopic dermatitis. Mometasone furoate, a moderate-potency steroid, produced significantly greater improvement than the low-potency hydrocortisone used twice daily. The difference in therapeutic response was particularly evident in patients with involvement of more than 25% of their body surface area. Morning plasma cortisol levels were assayed before treatment, after 1 week of therapy, and at the end of the clinical trial. Plasma cortisol levels were transiently suppressed in one child who was treated with hydrocortisone and in none of the children treated with mometasone.     

A double-blind comparison of sulconazole nitrate 1% cream with clotrimazole 1% cream in the treatment of dermatophytoses

Forty patients with dermatophytosis were treated with either sulconazole 1% cream or clotrimazole 1% cream (twenty patients in each group) twice daily for 4 weeks. Overall clinical improvement with respect to baseline at weeks 2, 3 and 4 favoured sulconazole-treated patients (the differences were statistically significant). The weekly mean severity scores for the sulconazole-treated patients for erythema, scaling, fissuring and itching were consistently lower than those for the clotrimazole-treated patients and the differences were statistically significant for erythema and sealing. It was concluded that sulconazole nitrate 1% cream is very effective against various dermatophytoses.     

Tazarotene 0.1% cream for the treatment of photodamage

Tazarotene (Tazorac, Allergan) has been shown to be effective in reducing the effects of photoaging in short term studies. To determine its effectiveness in the longer term, a 24-week multicenter, double-blind, randomized, vehicle controlled intervention study of 562 patients with facial photodamage was carried out followed by a 28-week open label extension. Patients were treated with one daily application of tazarotene 0.1% cream or vehicle cream to the face for 24 weeks, then tazarotene 0.1% cream for another 28 weeks. At week 24, when compared to vehicle, tazarotene resulted in a significantly greater incidence of patients achieving treatment success (over 50 percent greater improvement) and at least a 1 grade improvement in fine wrinkling, mottled pigmentation, pore size, lentigines, elastosis, irregular depigmentation, tactile roughness, coarse wrinkling and overall integrated assessment of photodamage. Additional clinical improvement occurred with continued tazarotene treatment and had not plateaued by week 52.     

盐酸特比萘芬乳膏1周与咪康唑乳膏1周、4周治疗趾间型足癣的多中心随机双盲研究

目的 探讨1％特比萘芬乳膏1周、2％硝酸咪康唑乳膏1周、4周治疗趾间型足癣的疗效、安全性及复发情况。方法 采用多中心、随机、双盲、平行对照法,入选患者分层随机分为3组,包括特比萘芬1周组(特比萘芬外用每日2次连续1周后再使用3周安慰剂)、咪康唑1周组(咪康唑每日2次连用1周+3周安慰剂)和咪康唑4周组(咪康唑每日2次连用4周),用药后第1、3、4、6、9、12周随访进行临床、真菌学评估。结果 152例真菌培养阳性的患者进入疗效分析。4周随访时,特比萘芬1周组,咪康唑4周组和咪康唑1周组的真菌治愈率分别为94.7％、87.8％和82.6％;3组综合疗效有效率分别89.5％、81.6％和63.0％;第12周随访时,3组真菌复发率分别为12.96％、13.95％和21.05％;不良反应发生率3组分别为2.38％、2.38％和3.57％。结论 外用1％特比萘芬乳膏1周治疗趾间型足癣与外用咪康唑乳膏4周疗效和复发率相近。     

Amorolfine spray in the treatment of foot mycoses (a dose-finding study)

Summary A total of 382 patients with foot mycosis were entered into a dose-finding study. Patients were randomly treated with amorolfine spray 0.5% or 2% (double-blind) or cream 0.5% (open; used as a reference agent). The spray or cream was applied once daily for 4 weeks on average. At screening, in 348 patients evaluable for efficacy, a total of 381 fungi were isolated: Trichopyton rubrum (196), T. mentagrophytes (73), other dermatophytes (17), Candida albicans (65), other yeasts (23), and moulds (7). In 33 patients the fungal infection was mixed. Two weeks after the end of treatment, the culture was negative in 94.1% and 97.4% of patients treated with 0.5% or 2% amorolfine spray, respectively. The difference was not statistically significant. In the 0.5% cream group the culture was negative in 86.6% of patients. Nine out of 380 patients evaluable for safety had local adverse events: four (3.2%) in each of the spray groups, and one (0.8%) in the cream group. The most common local adverse events in the patients treated with spray were a burning sensation and dryness of the skin. In conclusion, both spray concentrations were highly efficacious and well tolerated. Further studies should show if more widely spaced treatment with amorolfine spray is as effective as daily administration.     

A double-blind study of 1% metronidazole cream versus systemic oxytetracycline therapy for rosacea

In a randomized double-blind trial fifty-one patients with rosacea were treated for 2 months with either 1% metronidazole cream and placebo tablets or with 250 mg oxytetracycline tablets taken twice daily, and placebo cream (the cream base). The patients were assessed before and at the end of the trial, using the following criteria: (1) overall clinical assessment, (2) lesion counts, (3) degree of erythema, (4) independent photographic evaluation, (5) patients' opinion. An improvement was shown in 90% of the patients of both groups, and there was no significant difference between the two treatments. One per cent metronidazole cream has been shown to be significantly better than a placebo cream in the treatment of rosacea (Gamborg Nielsen, 1983a), It was therefore considered important to compare the cream with conventional therapy, and for this reason a double-blind study of 1% metronidazole cream versus a daily dose of 500 mg oxytetracycline was performed.     

A randomized trial of amorolfine 5% solution nail lacquer combined with oral terbinafine compared with terbinafine alone in the treatment of dermatophytic toenail onychomycoses affecting the matrix region

In view of recent advances in the development of antifungal agents, this study examined the possible synergy of two new antifungal agents, terbinafine and amorolfine. The study compared two different courses of terbinafine treatment combined with amorolfine 5% solution nail lacquer. Terbinafine was given orally for 6 (AT6 group) or 12 weeks (AT12 group) and amorolfine nail lacquer applied weekly for 15 months. A control group received terbinafine alone for 12 weeks. This was a randomized, prospective, open study of severe dermatophyte toenail onychomycosis with matrix region involvement. Nail samples were taken before the start of the study, at inclusion and at the visits at 6 weeks, 3, 9, 15 and 18 months. To assess the value of such combined therapy we chose an early parameter as the principal outcome variable, which was the result of mycological examination, including direct microscopy and culture, at 3 months (allowing a margin of 15 days). The secondary parameters of success were the mycological results at the later visits, clinical evaluation and a combined mycological-clinical response. Safety and tolerance were also assessed. Adverse events were recorded and liver function tests were performed monthly during the terbinafine treatment. Of the 147 patients included in the trial, 121 attended the 3-month visit, within a time limit of 15 days of 3 months after the beginning of treatment: 40 in the AT6 group, 40 in the AT12 group and 41 in the control group. In all, 32 of 121 patients (26. 4%) had negative mycological results on direct microscopy and culture: 14 of 40 (35.0%) in the AT6 group, 11 of 40 (27.5%) in the AT12 group and seven of 41 (17.1%) in the control group. The cure rate for the global (mycological and clinical cure) response measured at 18 months in 145 patients was 44.0% (22 patients) in the AT6 group, 72.3% (34 patients) in the AT12 group and 37.5% (18 patients) in the terbinafine group. These results suggest that the combination of amorolfine and terbinafine may be of value in the treatment of severe onychomycosis. At the same time a pilot pharmacoeconomic analysis was performed demonstrating a better cost per cure ratio for the patients receiving combination treatment.     

利拉萘酯乳膏治疗体股癣及足癣的多中心随机双盲对照观察

目的 探讨2%利拉萘酯乳膏治疗体股癣、足癣的临床疗效和安全性。方法 采用多中心随机双盲阳性药平行对照法，分别在3个中心进行，入选288例患者，2%利拉萘酯乳膏试验组144例，1% 联苯苄唑乳膏对照组144例；每组中体股癣患者各72例，足癣患者各72例。每日涂药1次，足癣疗程4周，每2周复诊1次；体股癣疗程2周，每周复诊1次；停药后2周均再复诊1次。结果 试验组体股癣患者中有１例脱落。停药时体股癣试验组的痊愈率和有效率分别为59.2%和94.4%，足癣试验组分别为41.7%和81.9%，与对照组比较，差异均无统计学意义（P ＞ 0.05）。在用药结束后2周时，体股癣试验组的痊愈率和有效率分别为67.6%和94.4%，足癣试验组分别为54.2%和81.9%，与对照组比较，差异无统计学意义（P ＞ 0.05）。在用药结束后2周，体股癣和足癣试验组符合方案分析集真菌学清除率分别为97.18%和90.28%，试验组和对照组差异均无统计学意义（P ＞ 0.05）。用药后发生的不良反应表现为用药部位红肿、疼痛，其中体股癣试验组不良反应发生率为2.78%。结论 2%利拉萘酯乳膏治疗体股癣、足癣有良好的疗效和安全性。     

Pimecrolimus 1% cream for cutaneous lupus erythematosus

Topical treatment of cutaneous lupus erythematosus usually includes potent glucocorticosteroids. However, prolonged use causes adverse side effects including skin atrophy as the foremost concern. In contrast to glucocorticosteroids, the anti-inflammatory and immunosuppressive macrolactam pimecrolimus has no atrophogenic potential. Affected areas of 11 patients with different forms of lupus erythematosus were treated with pimecrolimus 1% cream under semiocclusive conditions twice daily for 3 weeks. Skin involvement before and after therapy was assessed by means of a clinical score. In all patients, significant regression of skin lesions was observed after therapy (P <.001). This was an open and uncontrolled study on a limited number of cases. We suggest that pimecrolimus 1% cream could be an efficacious and safe treatment option for cutaneous lupus erythematosus.