Seyedmousavi Seyedmojtaba, Verweij Paul E, Mouton Johan W
Department of Medical Microbiology and Infectious Diseases, Erasmus MC, P.O. Box. 2040, 3000 CA, Rotterdam, The Netherlands.
Expert Rev Anti Infect Ther. 2015 Jan;13(1):9-27. doi: 10.1586/14787210.2015.990382.
The prodrug isavuconazonium sulfate (BAL8557) is an extended-spectrum water-soluble triazole, developed for the treatment of severe invasive and life-threatening fungal diseases. Its active moiety, BAL4815, is a potent inhibitor of ergosterol biosynthesis, resulting in the disruption of fungal membrane structure and function. The active compound shows broad-spectrum of activity and potency against all major opportunistic fungi, such as Aspergillus spp., Candida spp., Cryptococcus spp., Mucorales, Black yeasts and their filamentous relatives and the true pathogenic fungi, including Histoplasma capsulatum and Blastomyces dermatitidis. It is currently in Phase III clinical development for treatment of aspergillosis, candidiasis and mucormycosis, as well as other rare fungi infections. We reviewed the pharmacokinetic and pharmacodynamic characteristics of isavuconazole, and its microbiological and clinical investigation progress in advanced stages of development.
前体药物硫酸艾沙康唑(BAL8557)是一种广谱水溶性三唑类药物,用于治疗严重的侵袭性和危及生命的真菌疾病。其活性部分BAL4815是麦角甾醇生物合成的强效抑制剂,导致真菌膜结构和功能的破坏。该活性化合物对所有主要的机会性真菌,如曲霉属、念珠菌属、隐球菌属、毛霉目、黑色酵母菌及其丝状亲缘菌以及真正的致病真菌,包括荚膜组织胞浆菌和皮炎芽生菌,均表现出广谱活性和效力。目前它正处于治疗曲霉病、念珠菌病和毛霉病以及其他罕见真菌感染的III期临床开发阶段。我们综述了艾沙康唑的药代动力学和药效学特征,以及其在开发后期的微生物学和临床研究进展。