title: Role of micafungin in the antifungal armamentarium.
abstract: Serious infections caused by opportunistic molds remain a major problem for public health. Immune deficiency following organ transplantation and aggressive cancer treatment has greatly increased the incidence of systemic mycoses, and invasive aspergillosis in patients with AIDS is associated with significant morbidity and mortality. Amphotericin B is the first-line therapy for systemic infection because of its broad-spectrum and fungicidal activity. However, considerable side effects limit its clinical utility. The echinocandins are large lipopeptide molecules that inhibit the synthesis of 1,3-beta-D-glucan, a key component of the fungal cell wall. Three echinocandins have reached the market, and some others are in early clinical development. Caspofungin was the first echinocandin to be licensed for clinical use in most countries. Micafungin is licensed for clinical use in Japan, China, Taiwan, Jordan, Korea, Hong-Kong and the US, and anidulafungin is currently licensed in the US. The novel class of echinocandins represents a milestone in antifungal drug research that has further expanded our therapeutic options. Studies to date have shown that micafungin exhibits extremely potent antifungal activity against clinically important fungi, including Aspergillus and azole-resistant strains of Candida. In animal studies, micafungin is as efficacious as amphotericin B with respect to improvement of survival rate. Micafungin is also characterized by a linear pharmacokinetic profile and substantially fewer toxic effects. Micafungin is a poor substrate for the cytochrome P450 enzymes, and compared to azoles, fewer drug interactions are described. No dose adjustments of the drug are required in the presence of mycophenolate mofetil, cyclosporin, tacrolimus, prednisolone, or sirolimus. Strategies using this new echinocandin agent will benefit a large number of patients with severe immune dysfunction.
authors.affiliation: Development Division, Astellas Pharma Inc. 3-17-1 Hasune, Tokyo 174-8612, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Ikeda
authors.forename: Shigeki
authors.initials: S
authors.lastname: Tanaka
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ohki
authors.forename: Satoru
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Maki
authors.forename: Masataka
authors.initials: M
authors.lastname: Katashima
authors.forename: David
authors.initials: D
authors.lastname: Barrett
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Aoki
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy; D002177:Candidiasis / Q000188:drug therapy; D002473:Cell Wall / Q000187:drug effects; D002986:Clinical Trials as Topic; D004347:Drug Interactions; D025141:Drug Resistance, Fungal; D054714:Echinocandins; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D053878:Hemolytic Agents / Q000138:chemical synthesis; D006801:Humans; D055666:Lipopeptides; D008074:Lipoproteins / Q000009:adverse effects / Q000627:therapeutic use*; D000077551:Micafungin; D051379:Mice; D009181:Mycoses / Q000188:drug therapy* / Q000517:prevention & control; D009894:Opportunistic Infections / Q000178:diet therapy*; D010456:Peptides, Cyclic / Q000009:adverse effects / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; C110368:FR 901379; D053878:Hemolytic Agents; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D000077551:Micafungin