Yamada H, Tsuda T, Watanabe T, Ohashi M, Murakami K, Mochizuki H
Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd., Shizuoka, Japan.
Antimicrob Agents Chemother. 1993 Nov;37(11):2412-7. doi: 10.1128/AAC.37.11.2412.
In vitro and in vivo antifungal activities of D0870 were evaluated in comparison with those of fluconazole. D0870, which is the R-enantiomer of ICI195,739, was found to be the mycologically active enantiomer by comparing the activities of D0870 with those of M16355 (S-enantiomer of ICI195,739). D0870 showed a broad spectrum of antifungal activity and MICs and minimum antibiotic concentrations 4- to 2,000-fold lower in synthetic amino acid medium (fungal) agar than those of fluconazole for various fungi. Although MICs of D0870 were affected by variation of the test conditions, such as type of medium, inoculum size of fungi, supplementation with fetal bovine serum, and pH of medium, they were consistently much lower than those of fluconazole under any condition. In vivo activities of D0870 in the systemic infection models with Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus in normal mice and in the mice immunosuppressed with cyclophosphamide or cortisone acetate were 2- to 7-fold and 3- to 89-fold greater than those of fluconazole, respectively. In these infection models in immunosuppressed mice, the therapeutic efficacy of D0870 was almost equivalent to that in normal mice, whereas the efficacy of fluconazole was 2- to 50-fold lower than that in normal mice.
将D0870的体外和体内抗真菌活性与氟康唑进行了比较评估。D0870是ICI195,739的R-对映体，通过比较D0870与M16355（ICI195,739的S-对映体）的活性，发现其为具有真菌学活性的对映体。D0870表现出广谱抗真菌活性，在合成氨基酸培养基（真菌）琼脂中，其对各种真菌的最低抑菌浓度（MICs）和最低杀菌浓度比氟康唑低4至2000倍。尽管D0870的MICs受测试条件变化的影响，如培养基类型、真菌接种量、胎牛血清补充以及培养基pH值，但在任何条件下其始终远低于氟康唑。在正常小鼠以及用环磷酰胺或醋酸可的松免疫抑制的小鼠中，针对白色念珠菌、新型隐球菌和烟曲霉的全身感染模型，D0870的体内活性分别比氟康唑高2至7倍和3至89倍。在免疫抑制小鼠的这些感染模型中，D0870的治疗效果与正常小鼠几乎相当，而氟康唑的效果比正常小鼠低2至50倍。
