Occidiofungin is a nonribosomally synthesized cyclic lipopeptide that possesses broad-spectrum antifungal properties at submicromolar concentrations. This report explores multiple routes of administration and formulations of occidiofungin, as well as its toxicity in mice. Further, infection studies were performed in mice to assess the application of occidiofungin for treating systemic and intravaginal yeast infections. Formulations for intravenous and intravaginal administration of occidiofungin were prepared. Pharmacokinetic analyses were performed in a murine model, and a liquid chromatography-mass spectrometry (LC-MS) method was developed and used to quantify occidiofungin in mouse plasma samples. Toxicological and histopathological analyses of two repeat-dose studies using occidiofungin were performed. In these animal models, following intravenous administration, a liposomal formulation of occidiofungin improved the half-life and peak plasma drug concentration over that with a liposome-free formulation. Two long-term repeat-dosing toxicity studies of occidiofungin indicated the absence of toxicity in organ tissues. Murine models of a systemic yeast infection and a vulvovaginal yeast infection were performed. The findings of the systemic infection study revealed limitations in the use of occidiofungin that may be alleviated with the development of novel structural analogs or with further formulation studies. The gel formulation of occidiofungin demonstrated improved efficacy over that of the commercial product Monistat 3 in a vulvovaginal candidiasis study. This report outlines the optimal routes of administration of occidiofungin and demonstrates minimal toxicity following chronic exposure. Further, the results of these studies provide a clear indication for the use of occidiofungin for the treatment of recurrent vulvovaginal candidiasis (RVVC), which is a serious and clinically relevant issue.

中文翻译：

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新型抗真菌药 occidiofungin 的配方、药理评价和疗效研究。

Occidiofungin 是一种非核糖体合成的环状脂肽，在亚微摩尔浓度下具有广谱抗真菌特性。本报告探讨了 occidiofungin 的多种给药途径和制剂，以及它对小鼠的毒性。此外，在小鼠中进行了感染研究，以评估 occidiofungin 在治疗全身性和阴道内酵母菌感染中的应用。制备了用于静脉内和阴道内施用 occidiofungin 的制剂。在小鼠模型中进行了药代动力学分析，并开发了液相色谱-质谱 (LC-MS) 方法并用于量化小鼠血浆样品中的 occidiofungin。对使用 occidiofungin 的两项重复剂量研究进行了毒理学和组织病理学分析。在这些动物模型中，静脉内给药后，occidiofungin 的脂质体制剂比无脂质体制剂改善了半衰期和峰值血浆药物浓度。occidiofungin 的两项长期重复给药毒性研究表明在器官组织中没有毒性。进行了全身酵母菌感染和外阴阴道酵母菌感染的小鼠模型。全身感染研究的结果揭示了 occidiofungin 使用的局限性，这可能会随着新型结构类似物的开发或进一步的制剂研究而得到缓解。在外阴阴道念珠菌病研究中，occidiofungin 的凝胶制剂显示出比商业产品 Monistat 3 更高的功效。本报告概述了 occidiofungin 的最佳给药途径，并证明长期接触后毒性极小。此外，这些研究的结果为使用 occidiofungin 治疗复发性外阴阴道念珠菌病 (RVVC) 提供了明确的指示，这是一个严重的临床相关问题。