title: Single or 2-Dose Micafungin Regimen for Treatment of Invasive Candidiasis: Therapia Sterilisans Magna!
abstract: The time the earth takes to rotate its axis (the day) has dictated how often pharmaceutical compounds are dosed. The scientific link between the 2 events is materia medica arcana. As an example, in the treatment of invasive candidiasis, antifungal therapy with intravenous micafungin is dosed daily. A literature review revealed population pharmacokinetic analyses, in vivo pharmacokinetics/pharmacodynamics studies, and maximum-tolerated-dose studies of micafungin that examined optimal micafungin dosing strategies. The half-life of micafungin in patient blood was 14 hours in several studies, but was even longer in different organs, so that the concentration will persist above minimum inhibitory concentrations of Candida species for several days. Studies in mice and rabbits with persistent neutropenia and disseminated candidiasis, otherwise fatal, demonstrated that a single large dose of micafungin could clear disseminated candidiasis, even though the micafungin half-life in such animals is shorter than in humans. Human pharmacokinetics/pharmacodynamics studies confirmed this link between micafungin efficacy and the ratio of the area under the concentration-time curve, and the optimal exposures initially identified in neutropenic animals. Maximum tolerated dose studies have demonstrated safety of 900 mg administered daily for several weeks, whereas case reports demonstrate efficacy and safety of single 1400-mg doses. Thus, a single dose of micafungin, or 2 such doses within a few days of each other, is not only logical, but might even lead to faster clearance of Candida.
authors.affiliation: Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.
authors.forename: Tawanda
authors.initials: T
authors.lastname: Gumbo
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002175:Candida / Q000187:drug effects; D058365:Candidiasis, Invasive / Q000188:drug therapy* / Q000382:microbiology; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D054714:Echinocandins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D055666:Lipopeptides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D020714:Maximum Tolerated Dose; D000077551:Micafungin; D051379:Mice; D008826:Microbial Sensitivity Tests; D011817:Rabbits
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077551:Micafungin
keywords: intermittent therapy; invasive candidiasis; maximum tolerated dose; micafungin; pharmacokinetics/pharmacodynamics