Profile of isavuconazole and its potential in the treatment of severe invasive fungal infections.
Profile of isavuconazole and its potential in the treatment of severe invasive fungal infections.
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DOI：
10.2147/idr.s51340
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发表时间：
2013-10-22
影响因子：
3.9
通讯作者：
Pasqualotto, Alessandro C
中科院分区：
文献类型：
--
作者：
Falci, Diego R;Pasqualotto, Alessandro C
三唑类抗真菌药物包括用于治疗几种侵袭性真菌疾病的一线药物。艾沙康唑是一种新型广谱三唑类药物。本文总结了其特点，并与目前可用的抗真菌药物进行了比较。艾沙康唑作为前药给药，并且是水溶性的。有口服和静脉注射制剂。考虑到环糊精的潜在肾毒性，其静脉制剂不含环糊精，这比伏立康唑更有优势。与其他唑类药物一样，艾沙康唑需要负荷剂量。由于其半衰期延长，每天一次的方案是可能的。考虑到艾沙康唑与其他三唑类药物具有相同的作用机制，交叉耐药性是该类药物的重要问题。耐受性和安全性特征是有利的，并且没有持续报告严重不良事件。预计与细胞色素P450代谢的药物发生显著相互作用，尤其是与CYP3A4酶的底物和诱导剂。艾沙康唑对大多数医学重要真菌具有体外活性，包括念珠菌属、曲霉属和隐球菌属。它对毛霉菌病的病原体有一定的活性。关于艾沙康唑的临床数据仍然有限，因为正在进行的试验尚未完成或发表。艾沙康唑有可能成为侵袭性曲霉病的一线治疗药物。它也有可能用于抗真菌预防、挽救治疗或联合治疗。临床试验的结果最终预期，以充分定位艾沙康唑在目前的抗真菌药物。
The triazole class of antifungal drugs comprises first-line agents for the treatment of several invasive fungal diseases. Isavuconazole is a novel broad-spectrum triazole agent. Here we summarize its characteristics and compare it with the currently available antifungal agents. Isavuconazole is administered as a prodrug, and it is water soluble. Oral and intravenous formulations are available. Its intravenous formulation does not contain cyclodextrin, which is an advantage over voriconazole, considering the potential for nephrotoxicity of cyclodextrin. As with other azoles, isavuconazole requires a loading dose. Due to its prolonged half-life, a once-a-day regimen is possible. Considering that isavuconazole shares the same mechanism of action with the other triazoles, cross-resistance is an important concern in the class. Tolerability and safety profiles are favorable, and no serious adverse events have been consistently reported. Significant interactions with drugs metabolized by cytochrome P450 are expected to occur, especially with substrates and inducers of the CYP3A4 enzyme. Isavuconazole has in vitro activity against most medically important fungi, including species of Candida, Aspergillus, and Cryptococcus. It has some activity against the agents of mucormycosis. Clinical data regarding isavuconazole remain limited because ongoing trials have not yet been completed or published. Isavuconazole has the potential to become first-line therapy for invasive aspergillosis. It also has the potential for use in the context of antifungal prophylaxis, salvage therapy, or in combination regimens. Results of clinical trials are ultimately expected in order to adequately position isavuconazole in the current antifungal armamentarium.