University of Iceland, Department of Dermatology, Smaratorg 1201, Kópavogur, Reykjavik, Iceland.
Expert Opin Investig Drugs. 2012 Oct;21(10):1549-62. doi: 10.1517/13543784.2012.711315. Epub 2012 Aug 9.
Current topical treatments for onychomycosis are unsatisfactory. New topical agents that offer efficacy without the potential adverse effects of oral antifungal therapy would benefit patients with this condition and encourage a greater treatment rate.
Currently available topical therapies are reviewed, and new approaches for enhancing delivery of the established antifungal terbinafine through the nail are summarized. We focus on the use of ultra-deformable lipid vesicles to facilitate delivery of terbinafine to the nail and surrounding tissue. TDT 067 (terbinafine in Transfersome) is the only such therapy in development for onychomycosis, and we review published preclinical and clinical studies on this formulation.
TDT 067 offers the use of new technology to deliver an established antifungal, terbinafine. Preclinical data suggest that the Transfersome accelerates entry of terbinafine released from TDT 067 into fungi and potentiates its antifungal effects, resulting in enhanced activity, compared with conventional terbinafine. This translated into high rates of mycological cure and evidence of clinical effect in a study of TDT 067 administered twice daily for 12 weeks in patients with onychomycosis. An ongoing Phase-III trial involving more than 700 patients treated for 48 weeks is investigating the efficacy and safety of TDT 067.
目前治疗甲真菌病的局部治疗方法并不令人满意。新的局部治疗药物如果能提供与口服抗真菌治疗相同的疗效，而没有潜在的不良反应，将使这种疾病的患者受益，并鼓励更高的治疗率。
本文回顾了目前可用于治疗甲真菌病的局部治疗方法，并总结了增强现有抗真菌药物特比萘芬在指甲内传递的新方法。我们专注于使用超变形脂质体来促进特比萘芬向指甲和周围组织的传递。TDT 067（特比萘芬在转铁蛋白中的制剂）是唯一一种用于治疗甲真菌病的此类药物，我们对该制剂的已发表的临床前和临床研究进行了综述。
TDT 067 提供了使用新技术来传递一种已有的抗真菌药物特比萘芬。临床前数据表明，转铁蛋白加速了 TDT 067 释放的特比萘芬进入真菌的速度，并增强了其抗真菌作用，与传统的特比萘芬相比，其活性更高。这在一项为期 12 周、每天两次使用 TDT 067 治疗甲真菌病患者的研究中转化为高的真菌学治愈率和临床疗效证据。一项涉及 700 多名患者、治疗 48 周的正在进行的 III 期试验正在研究 TDT 067 的疗效和安全性。
