Tachibana Haruki, Kumagai Naomichi, Tatsumi Yoshiyuki
Pharmacology Department, Drug Research Center, Kaken Pharmaceutical Co., Ltd. 14, Shinomiya, Minamigawara-cho, Yamashina-ku, Kyoto 607-8042, Japan.
J Fungi (Basel). 2017 Oct 19;3(4):58. doi: 10.3390/jof3040058.
Use of oral antifungals in the treatment of onychomycosis is commonplace; but their use can be limited by safety and patient concerns. Due to their broader safety margins, topical antifungals (efinaconazole, tavaborole, and ciclopirox) are a useful option in the treatment of mild-to-moderate onychomycosis in the USA, but their antifungal activity has yet to be directly compared. This study aims to identify important factors contributing to in vivo efficacies of the three topical antifungals. Minimum inhibitory concentrations (MICs) were determined by Clinical and Laboratory Standards Institute (CLSI) M38-A2 broth microdilution. The MIC values of efinaconazole, tavaborole, and ciclopirox for were 0.0078, 8.0, and 0.50 μg/mL, respectively. The MIC values for were 0.016, 8.0, and 0.50 μg/mL, respectively. Efinaconazole showed potent fungicidal activity in keratin-containing medium, whereas tavaborole was fungistatic, and ciclopirox not active. In the guinea pig model of onychomycosis, the therapeutic efficacy of efinaconazole was superior to those of tavaborole and ciclopirox. This study suggests that not only fungistatic activity (MIC), but also fungicidal activity in the presence of keratin, is an important factor contributing to the in vivo efficacy of topical antifungal drugs against onychomycosis.
口服抗真菌药物用于治疗甲癣很常见；但其使用可能受到安全性和患者顾虑的限制。由于局部用抗真菌药物（艾氟康唑、他伏硼罗和环吡酮）具有更宽的安全范围，在美国它们是治疗轻至中度甲癣的有用选择，但它们的抗真菌活性尚未得到直接比较。本研究旨在确定影响这三种局部用抗真菌药物体内疗效的重要因素。最低抑菌浓度（MIC）通过临床和实验室标准协会（CLSI）M38 - A2肉汤微量稀释法测定。艾氟康唑、他伏硼罗和环吡酮对 的MIC值分别为0.0078、8.0和0.50 μg/mL。对 的MIC值分别为0.016、8.0和0.50 μg/mL。艾氟康唑在含角蛋白的培养基中显示出强效杀菌活性，而他伏硼罗是抑菌性的，环吡酮无活性。在甲癣豚鼠模型中，艾氟康唑的治疗效果优于他伏硼罗和环吡酮。本研究表明，不仅抑菌活性（MIC），而且在有角蛋白存在时的杀菌活性，都是影响局部用抗真菌药物治疗甲癣体内疗效的重要因素。
