title: Caspofungin acetate: an antifungal agent.
abstract: The pharmacology, bioavailability and pharmacokinetics, clinical efficacy, and adverse effects of caspofungin acetate are reviewed. Caspofungin acetate is an echinocandin with fungicidal activity against a wide range of pathogens, including Candida spp., Aspergillus spp., and Histoplasma spp. It is active against fluconazole-resistant and fluconazole-susceptible strains of Candida albicans. Caspofungin acetate irreversibly inhibits the enzyme 1,3-beta-D-glucan synthase, preventing the formation of glucan polymers and disrupting the integrity of the fungal cell wall. Caspofungin acetate has an elimination half-life of 9-10 hours and is suitable for once-daily regimens. Data from animal and human studies demonstrate that the drug is 80-96% protein bound. Less than 3% of the dose is eliminated unchanged in the urine, and the proposed route of elimination is hepatic. In a trial of 128 patients with Candida esophagitis, clinical response rates were higher with caspofungin acetate 50 or 70 mg/day (85%) than with amphotericin B 0.5 mg/kg/day (67%). Most enrolled patients had HIV infection, and almost half had CD4+ lymphocyte counts of less than 50 cells/microL in another study, 56 immunocompromised patients with aspergillosis were treated with one 70-mg dose of caspofungin acetate, then 50 mg once a day. All patients had refractory invasive aspergillosis or were intolerant of amphotericin B, liposomal amphotericin B, or azole therapy. In patients who received at least one dose of caspofungin acetate, a favorable response was reported in 41%. In 128 patients who received either caspofungin acetate or amphotericin B, fewer caspofungin acetate recipients (1.4%) had elevated serum creatinine levels and discontinued therapy because of adverse effects (4%) than amphotericin B recipients (15% and 22%, respectively). The manufacturer's recommended dose for infections caused by Candida or Aspergillus spp. has not been determined. Caspofungin acetate appears to be fungicidal, with a wide spectrum of antifungal activity and a good safety profile. The lack of adequate efficacy and safety data in humans makes a recommendation to add this drug to the formulary premature. Pending advanced clinical trials and cost information, caspofungin acetate may be a reasonable addition to the formulary, particularly in hospitals with large immunocompromised patient populations.
authors.affiliation: New York Presbyterian-New York Weill Cornell Center, New York, USA.
authors.forename: A
authors.initials: A
authors.lastname: Hoang
mesh_terms: D000328:Adult; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001682:Biological Availability; D000077336:Caspofungin; D004347:Drug Interactions; D054714:Echinocandins; D005658:Fungi / Q000187:drug effects*; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000188:drug therapy*; D010455:Peptides; D010456:Peptides, Cyclic
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D010455:Peptides; D010456:Peptides, Cyclic; D000077336:Caspofungin