SCY-078, a Novel Fungicidal Agent, Demonstrates Distribution to Tissues Associated with Fungal Infections during Mass Balance Studies with Intravenous and Oral [ 14 C]SCY-078 in Albino and Pigmented Rats

Antimicrob Agents Chemother. 2019 Jan 29;63(2):e02119-18. doi: 10.1128/AAC.02119-18. Print 2019 Feb.

Abstract

SCY-078, a fungicidal β-1,3-glucan synthesis inhibitor administered as intravenous or oral [14C]SCY-078 to rats, was distributed primarily into tissues associated with invasive fungal disease (kidney, lung, liver, spleen, bone marrow, muscle, vaginal tissue, and skin) to levels exceeding those in plasma. Oral fraction absorbed was ∼40%. Elimination was primarily via bile and feces (∼90%) and urine (∼1.5%). Mean half-time was ∼8 h. Quantitative whole-body autoradiography showed a rapid distribution at 8 h and elimination by 168 h postdose.

Keywords: antifungal agents; mass balance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents / blood*
  • Antifungal Agents / pharmacokinetics*
  • Antifungal Agents / therapeutic use
  • Area Under Curve
  • Aspergillus / drug effects
  • Candida / drug effects
  • Female
  • Glycosides / blood*
  • Glycosides / pharmacokinetics*
  • Glycosides / therapeutic use
  • Male
  • Mycoses / drug therapy
  • Rats
  • Rats, Wistar
  • Tissue Distribution
  • Triterpenes / blood*
  • Triterpenes / pharmacokinetics*
  • Triterpenes / therapeutic use

Substances

  • Antifungal Agents
  • Glycosides
  • Triterpenes
  • ibrexafungerp