Clinical Pharmacokinetics and Drug-Drug Interaction Potential for Coadministered SCY-078, an Oral Fungicidal Glucan Synthase Inhibitor, and Tacrolimus

Clin Pharmacol Drug Dev. 2019 Jan;8(1):60-69. doi: 10.1002/cpdd.588. Epub 2018 Jun 27.


SCY-078 is an orally bioavailable triterpenoid glucan synthase inhibitor in clinical development as an intravenous and oral treatment of fungal infections caused by Candida and Aspergillus species. This was a sequential, single-center, open-label phase 1 study to assess the drug-drug interaction potential between SCY-078 and tacrolimus during concomitant administration in healthy subjects. In cohort 1, period 1, subjects received a single oral dose of tacrolimus 2 mg in the fasted state. In period 2 after a ≥15 day washout, subjects received a single loading dose of SCY-078 1250 mg on day 1 followed by maintenance doses of SCY-780 750 mg on days 2 through 8. On day 3 of period 2, subjects also received a single dose of tacrolimus 2 mg concurrent with SCY-078. In cohort 2, subjects received a loading dose of SCY-078 1250 mg on day 1 followed by maintenance doses of SCY-780 750 mg on days 2 and 3. Pharmacokinetic (PK) parameters were compared to assess both the impact of steady-state SCY-078 on tacrolimus and the impact of tacrolimus on the PK of steady-state SCY-078. The concurrent coadministration of tacrolimus and SCY-078 had no effect on the maximum blood levels of tacrolimus, as evidenced by no change in maximum concentration of drug in blood plasma and a 1.4-fold increase in total area under the plasma drug concentration-time curve. The concurrent coadministration of tacrolimus and SCY-078 resulted in a weaker interaction than typically observed with the azole class of antifungals. The current data indicate that an initial dose adjustment for tacrolimus may not be warranted when combined with SCY-078, as the modest increase in exposure is less than the therapeutic window, although tacrolimus monitoring, as with addition of any new medication, is recommended. These results support the coadministration of SCY-078 and tacrolimus.

Keywords: antifungal; drug interaction; pharmacokinetics; pharmacology; tacrolimus.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Antifungal Agents / adverse effects
  • Antifungal Agents / blood
  • Antifungal Agents / pharmacokinetics*
  • Antifungal Agents / pharmacology
  • Drug Interactions
  • Glucosyltransferases / antagonists & inhibitors
  • Glycosides / adverse effects
  • Glycosides / blood
  • Glycosides / pharmacokinetics*
  • Glycosides / pharmacology
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / blood
  • Immunosuppressive Agents / pharmacokinetics*
  • Immunosuppressive Agents / pharmacology
  • Male
  • Tacrolimus / adverse effects
  • Tacrolimus / blood
  • Tacrolimus / pharmacokinetics*
  • Tacrolimus / pharmacology
  • Triterpenes / adverse effects
  • Triterpenes / blood
  • Triterpenes / pharmacokinetics*
  • Triterpenes / pharmacology


  • Antifungal Agents
  • Glycosides
  • Immunosuppressive Agents
  • Triterpenes
  • ibrexafungerp
  • Glucosyltransferases
  • glucan synthase
  • Tacrolimus