Kartsonis Nicholas A, Nielsen Jennifer, Douglas Cameron M
Merck Research Laboratories, BL 3-4, P.O. Box 4, West Point, PA 19486-0004, USA.
Drug Resist Updat. 2003 Aug;6(4):197-218. doi: 10.1016/s1368-7646(03)00064-5.
Caspofungin is the first approved agent from a new class of antifungals, the echinocandins. By targeting the fungal cell wall (as opposed to the fungal cell membrane), the echinocandins exhibit a unique mechanism of action relative to the other currently approved antifungal agents. Preclinical (in vitro and in vivo) studies have demonstrated activity for caspofungin against the most commonly encountered fungi in the hospital setting, namely Candida and Aspergillus species. Caspofungin is administered as a once-a-day, intravenous formulation. Notably, caspofungin is neither an inhibitor, inducer, nor metabolite of the cytochrome p450 system. To date, few drug-drug interactions have been seen for this echinocandin. A number of Phase II and III clinical studies in documented invasive candidiasis, esophageal candidiasis, and invasive aspergillosis have been completed and have demonstrated efficacy for caspofungin against all three diseases. In all studies, caspofungin manifested an excellent safety profile with few serious, drug-related adverse events or discontinuations due to drug-related adverse events. Isolated symptoms compatible with histamine release have been infrequently reported. In clinical studies, drug-related nephrotoxicity with caspofungin has been rare, and the incidence of liver transaminase elevations has been similar to the incidence seen with comparator agents. Results from a Phase III study as empirical therapy in patients with febrile neutropenia are anticipated in late 2003. Overall, caspofungin represents an important addition to the current antifungal armamentarium.
卡泊芬净是新型抗真菌药物棘白菌素类中首个获批的药物。与其他目前获批的抗真菌药物相比,棘白菌素类通过作用于真菌细胞壁(而非真菌细胞膜)展现出独特的作用机制。临床前(体外和体内)研究已证明卡泊芬净对医院环境中最常见的真菌,即念珠菌属和曲霉属具有活性。卡泊芬净采用每日一次的静脉制剂给药。值得注意的是,卡泊芬净既不是细胞色素P450系统的抑制剂、诱导剂,也不是其代谢产物。迄今为止,这种棘白菌素类药物几乎未见药物相互作用。多项关于确诊的侵袭性念珠菌病、食管念珠菌病和侵袭性曲霉病的II期和III期临床研究已经完成,证明卡泊芬净对这三种疾病均有效。在所有研究中,卡泊芬净表现出极佳的安全性,很少出现严重的、与药物相关的不良事件,也很少因药物相关不良事件而停药。与组胺释放相符的孤立症状报告较少。在临床研究中,卡泊芬净相关的药物性肾毒性很少见,肝转氨酶升高的发生率与对照药物相似。预计2003年末会有一项III期研究的结果,即卡泊芬净作为发热性中性粒细胞减少患者经验性治疗的结果。总体而言,卡泊芬净是目前抗真菌药物库中的一项重要补充。