抗真菌药物艾沙康唑研究进展

Progress in research of isavuconazole,a new antifungal agent

艾沙康唑是一种新的三唑类广谱抗真菌药，已被美国FDA授予快速审批资格、合格传染病产品资格认定和孤儿药地位认定。体外研究显示，艾沙康唑具有广谱抗真菌作用，包括酵母菌（如念珠菌属）和霉菌（如曲霉属、毛霉属）。艾沙康唑以水溶性前药（isavuconazonium sulfate）的形式静脉注射或口服给药，其半衰期较长（静脉注射为76～104h和口服为56～77h），仅需每目给药1次。一项治疗侵袭性曲霉菌病的Ⅲ期临床试验显示，艾沙康唑的疗效不劣于伏立康唑，艾沙康唑治疗相关的肝胆、皮肤以及眼部等器官紊乱的不良反应发生率明显少于伏立康唑。艾沙康唑分子中含有两个手性中心，目前已有多篇文献报道了相关合成方法。本文综述了艾沙康唑的体外抗菌活性、药动学、临床研究以及化学合成研究进展。

Isavuconazole is a novel broad-spectrum triazoleantifungal agent. It was granted the fast-track status and designated Qualified Infectious Disease Product （QIDP）, and an orphan drug for the treatment of inva- sive aspergillosis and mucormycosis by the U.S. Food and Drug Administration （FDA）. Isavueonazole demonstra- ted in vitro coverage of a broad range of yeasts （ such as Candida species） and molds （ such as Aspergillus species and Mucor species）. Isavuconazole is administered as a water-soluble prodrug. Oral and intravenous formulations are available. Due to its prolonged half-life（iv： t1/2 =76 -104 h, po： t1/2 = 56 ～ 77 h） , an once-a-day regimen is possible. In the phase III invasive aspergillosis study, isavuconazole demonstrated non-inferiority to voriconazole. Isavuconazole treatment-relevant adverse events were statistically fewer than voriconazole in the System Organ Clas- ses of hepatobiliary, skin and eye disorders. Isavuconazole contains two adjacent chiral centers, some patents have reported in synthesis of enantiomerically pure compounds. In this article, in vitro antibacterial activity, pharmaco- kinetic, clinical study and chemical synthesis of isavuconazole were reviewed.