Azole antifungal agents

Abstract

The discovery of the antifungal activity of azole compounds represented an important therapeutic advance. Miconazole, ketoconazole, and fluconazole are currently commercially available, and itraconazole has undergone extensive clinical evaluation. Because of its limited activity and toxicity, miconazole has been replaced by newer agents. Ketoconazole has proven useful in therapy for superficial infections and invasive infections caused by the pathogenic fungi. Among its disadvantages are limited absorption in the absence of gastric acid and its potential for drug-drug interactions. Fluconazole is the only azole available as oral and intravenous preparations. Unlike other azoles, it is only minimally metabolized in the liver and largely excreted in the urine as active drug. It is more effective than ketoconazole against superficial candidal infections and is the drug of choice for maintenance therapy for cryptococcal meningitis in patients infected with human immunodeficiency virus. An advantage of itraconazole is its activity against aspergillosis. It is also active against many infections caused by pathogenic fungi. Other azole compounds are at varying stages of preclinical and clinical investigation.