Rezafungin treatment in mouse models of invasive candidiasis and aspergillosis: Insights on the PK/PD pharmacometrics of rezafungin efficacy

Pharmacol Res Perspect. 2019 Nov 20;7(6):e00546. doi: 10.1002/prp2.546. eCollection 2019 Dec.

Abstract

Rezafungin acetate is a novel echinocandin in clinical development for prevention and treatment of invasive fungal infections. Rezafungin is differentiated by a pharmacokinetic/pharmacodynamic (PK/PD) profile that includes a long half-life allowing once-weekly administration, front-loaded plasma drug exposures associated with antifungal efficacy, and penetration into deep-seated infections, such as intra-abdominal abscesses. In this series of in vivo studies, rezafungin demonstrated efficacy in the treatment of neutropenic mouse models of disseminated candidiasis, including infection caused by azole-resistant Candida albicans, and aspergillosis. These results contribute to a growing body of evidence demonstrating the antifungal efficacy and potential utility of rezafungin in the treatment of invasive fungal infections.

Keywords: Aspergillus; CD101; Candida; antifungal treatment; azole resistance; echinocandin; in vivo efficacy; invasive aspergillosis; invasive candidiasis; rezafungin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / pharmacokinetics*
  • Aspergillosis / drug therapy*
  • Aspergillosis / immunology
  • Aspergillosis / microbiology
  • Aspergillus fumigatus / drug effects
  • Aspergillus fumigatus / isolation & purification
  • Candida albicans / drug effects
  • Candida albicans / isolation & purification
  • Candidiasis, Invasive / blood
  • Candidiasis, Invasive / drug therapy*
  • Candidiasis, Invasive / immunology
  • Candidiasis, Invasive / microbiology
  • Disease Models, Animal
  • Drug Administration Schedule
  • Echinocandins / administration & dosage
  • Echinocandins / pharmacokinetics*
  • Female
  • Half-Life
  • Humans
  • Immunocompromised Host
  • Male
  • Mice
  • Microbial Sensitivity Tests
  • Neutropenia / immunology

Substances

  • Antifungal Agents
  • Echinocandins
  • Rezafungin