Abstract：
BACKGROUND: Topical antifungals for toenail onychomycosis must penetrate the nail to deliver an inhibitory concentration of free drug to the site of infection. In two ex vivo experiments, we tested the ability of topical antifungals to inhibit growth of Trichophyton rubrum and Trichophyton mentagrophytes, the most common causative fungi in toenail onychomycosis.
METHODS: Seven topical antifungals were tested: three U.S. Food and Drug Administration-approved products indicated for onychomycosis (ciclopirox 8% lacquer; efinaconazole 10% solution; tavaborole 5% solution) and four over-the-counter (OTC) products for fungal infections (tolnaftate 1% and/or undecylenic acid 25% solutions). The ability to inhibit fungal growth was tested in the presence and absence of keratin. Products were applied either to human cadaverous nails or keratin-free cellulose disks prior to placement on an agar plate (radius: 85 mm) seeded with a clinical isolate of T. rubrum or T. mentagrophytes. After incubation, the zone of inhibition (ZI), defined as the radius of the area of no fungal growth, was recorded.
RESULTS: In the nail penetration assay, average ZIs for efinaconazole (T. rubrum: 82.1 mm; T. mentagrophytes: 63.8 mm) were significantly greater than those for tavaborole (63.5 mm; 39.1 mm), ciclopirox (7.4 mm; 3.6 mm) and all OTC products (range: 10.5-34.2 mm against both species; all P < 0.001). In the cellulose disk diffusion assay, efinaconazole and tavaborole demonstrated maximal antifungal activity against both species (ZIs = 85 mm); average ZIs against T. rubrum and T. mentagrophytes were smaller for ciclopirox (59.0 and 55.7 mm, respectively) and OTC products (range: 31.2-57.8 mm and 25.7-47.7 mm, respectively).
CONCLUSIONS: Among all antifungals tested, the ability to penetrate human toenails to inhibit growth of both T. rubrum and T. mentagrophytes was greatest for efinaconazole, followed by tavaborole. These results indicate superior transungual penetration of efinaconazole compared to the other antifungals, suggesting lower keratin binding in the nail.
METHODS: Seven topical antifungals were tested: three U.S. Food and Drug Administration-approved products indicated for onychomycosis (ciclopirox 8% lacquer; efinaconazole 10% solution; tavaborole 5% solution) and four over-the-counter (OTC) products for fungal infections (tolnaftate 1% and/or undecylenic acid 25% solutions). The ability to inhibit fungal growth was tested in the presence and absence of keratin. Products were applied either to human cadaverous nails or keratin-free cellulose disks prior to placement on an agar plate (radius: 85 mm) seeded with a clinical isolate of T. rubrum or T. mentagrophytes. After incubation, the zone of inhibition (ZI), defined as the radius of the area of no fungal growth, was recorded.
RESULTS: In the nail penetration assay, average ZIs for efinaconazole (T. rubrum: 82.1 mm; T. mentagrophytes: 63.8 mm) were significantly greater than those for tavaborole (63.5 mm; 39.1 mm), ciclopirox (7.4 mm; 3.6 mm) and all OTC products (range: 10.5-34.2 mm against both species; all P < 0.001). In the cellulose disk diffusion assay, efinaconazole and tavaborole demonstrated maximal antifungal activity against both species (ZIs = 85 mm); average ZIs against T. rubrum and T. mentagrophytes were smaller for ciclopirox (59.0 and 55.7 mm, respectively) and OTC products (range: 31.2-57.8 mm and 25.7-47.7 mm, respectively).
CONCLUSIONS: Among all antifungals tested, the ability to penetrate human toenails to inhibit growth of both T. rubrum and T. mentagrophytes was greatest for efinaconazole, followed by tavaborole. These results indicate superior transungual penetration of efinaconazole compared to the other antifungals, suggesting lower keratin binding in the nail.
摘要：
背景：用于趾甲甲癣的局部抗真菌剂必须穿透指甲以将抑制浓度的游离药物递送到感染部位。在两个离体实验中，我们测试了局部抗真菌药抑制红色毛癣菌和毛癣菌生长的能力，趾甲真菌病中最常见的致病真菌。
方法：测试了七种局部抗真菌药：三种美国食品和药物管理局批准的用于甲癣的产品（8％环吡酮漆；10％艾氟康唑溶液；5％他沃洛尔溶液）和四种用于真菌感染的非处方（OTC）产品（1％托萘泰特和/或25％十一碳烯酸溶液）。在存在和不存在角蛋白的情况下测试抑制真菌生长的能力。将产品施加到人尸体指甲或无角蛋白的纤维素盘上，然后放置在接种了红花T.rubrum或T.mentagrosphytes临床分离株的琼脂平板（半径：85mm）上。孵化后,抑制区(ZI)，定义为没有真菌生长的区域的半径，被记录下来。
结果：在指甲渗透试验中，艾菲康唑的平均ZIs(T.红斑：82.1毫米；T.动力植物：63.8毫米）显着大于tavaborole（63.5毫米；39.1毫米），环吡酮（7.4毫米;3.6毫米）和所有OTC产品（范围：10.5-34.2毫米，对两种物种；所有P<0.001）。在纤维素圆盘扩散测定中，依菲康唑和他沃博罗对这两种物种均表现出最大的抗真菌活性（ZIs=85mm）；环吡酮对红斑T.rubrum和T.mentagrophytes的平均ZIs较小（59.0和55.7mm，分别）和OTC产品（范围：31.2-57.8毫米和25.7-47.7毫米，分别)。
结论：在所有测试的抗真菌药物中，依菲康唑能够穿透人类脚趾甲以抑制红花T.rubrum和斑叶T.其次是塔沃博罗。这些结果表明，与其他抗真菌药相比，艾菲康唑的穿透性更高，提示指甲中角蛋白结合较低。
方法：测试了七种局部抗真菌药：三种美国食品和药物管理局批准的用于甲癣的产品（8％环吡酮漆；10％艾氟康唑溶液；5％他沃洛尔溶液）和四种用于真菌感染的非处方（OTC）产品（1％托萘泰特和/或25％十一碳烯酸溶液）。在存在和不存在角蛋白的情况下测试抑制真菌生长的能力。将产品施加到人尸体指甲或无角蛋白的纤维素盘上，然后放置在接种了红花T.rubrum或T.mentagrosphytes临床分离株的琼脂平板（半径：85mm）上。孵化后,抑制区(ZI)，定义为没有真菌生长的区域的半径，被记录下来。
结果：在指甲渗透试验中，艾菲康唑的平均ZIs(T.红斑：82.1毫米；T.动力植物：63.8毫米）显着大于tavaborole（63.5毫米；39.1毫米），环吡酮（7.4毫米;3.6毫米）和所有OTC产品（范围：10.5-34.2毫米，对两种物种；所有P<0.001）。在纤维素圆盘扩散测定中，依菲康唑和他沃博罗对这两种物种均表现出最大的抗真菌活性（ZIs=85mm）；环吡酮对红斑T.rubrum和T.mentagrophytes的平均ZIs较小（59.0和55.7mm，分别）和OTC产品（范围：31.2-57.8毫米和25.7-47.7毫米，分别)。
结论：在所有测试的抗真菌药物中，依菲康唑能够穿透人类脚趾甲以抑制红花T.rubrum和斑叶T.其次是塔沃博罗。这些结果表明，与其他抗真菌药相比，艾菲康唑的穿透性更高，提示指甲中角蛋白结合较低。
