Sucher Allana J, Chahine Elias B, Balcer Holly E
Lloyd L. Gregory School of Pharmacy, Palm Beach Atlantic University, West Palm Beach, FL, USA.
Ann Pharmacother. 2009 Oct;43(10):1647-57. doi: 10.1345/aph.1M237. Epub 2009 Sep 1.
To review the mechanism of action, antifungal spectrum of activity, pharmacodynamics, pharmacokinetics, clinical efficacy, and safety of the echinocandins.
A MEDLINE search (1982-May 2009) was conducted for articles published in the English language using the key words caspofungin, micafungin, anidulafungin, and echinocandins.
Medicinal chemistry, in vitro, and animal studies, as well as human trials were reviewed for information on the pharmacodynamics, pharmacokinetics, efficacy, and safety of each echinocandin. Clinical trials were reviewed and included to compare and contrast the available echinocandins.
Three echinocandin antifungal agents are currently approved for use in the US: caspofungin, micafungin, and anidulafungin. The echinocandins have a unique mechanism of action, inhibiting beta-(1,3)-D-glucan synthase, an enzyme that is necessary for the synthesis of an essential component of the cell wall of several fungi. The echinocandins display fungistatic activity against Aspergillus spp. and fungicidal activity against most Candida spp., including strains that are fluconazole-resistant. The echinocandins have been shown to be efficacious for the treatment of esophageal candidiasis, candidemia, and invasive candidiasis. In addition, caspofungin has demonstrated efficacy as empiric treatment of febrile neutropenia and salvage therapy for the treatment of invasive aspergillosis, and it is the only echinocandin approved for use in pediatric patients. Micafungin is the only echinocandin approved for use as prophylaxis against Candida infections in patients undergoing hematopoietic stem cell transplantation. Overall, resistance to echinocandins is still rare, and all agents are well tolerated, with similar adverse effect profiles and few drug-drug interactions.
Echinocandins, the newest addition to the arsenal of antifungals, offer potential advantages over other classes of agents. Clinicians should assess their distinguishing characteristics, including route of metabolism, drug interaction profile, and approved indications for use, when determining which agent to include on a formulary.
综述棘白菌素类药物的作用机制、抗真菌谱、药效学、药代动力学、临床疗效及安全性。
利用关键词卡泊芬净、米卡芬净、阿尼芬净和棘白菌素类，检索1982年至2009年5月发表在英文期刊上的文章。
综述了药物化学、体外及动物研究以及人体试验，以获取每种棘白菌素类药物的药效学、药代动力学、疗效及安全性方面的信息。对临床试验进行了综述，并纳入其中以比较和对比现有的棘白菌素类药物。
目前美国已批准三种棘白菌素类抗真菌药物用于临床：卡泊芬净、米卡芬净和阿尼芬净。棘白菌素类药物具有独特的作用机制，可抑制β-(1,3)-D-葡聚糖合成酶，该酶是几种真菌细胞壁重要成分合成所必需的一种酶。棘白菌素类药物对曲霉属真菌具有抑菌活性，对多数念珠菌属真菌具有杀菌活性，包括对氟康唑耐药的菌株。棘白菌素类药物已被证明对治疗食管念珠菌病、念珠菌血症及侵袭性念珠菌病有效。此外，卡泊芬净已证明对发热性中性粒细胞减少症的经验性治疗及侵袭性曲霉病的挽救治疗有效，且它是唯一被批准用于儿科患者的棘白菌素类药物。米卡芬净是唯一被批准用于预防造血干细胞移植患者念珠菌感染的棘白菌素类药物。总体而言，对棘白菌素类药物的耐药性仍然罕见，所有药物耐受性良好，不良反应谱相似，药物相互作用少。
棘白菌素类药物是抗真菌药物库中的最新成员，与其他类药物相比具有潜在优势。临床医生在确定将哪种药物纳入处方时，应评估其独特特征，包括代谢途径、药物相互作用情况及批准的适应证。
