Metabolism, Excretion, and Pharmacokinetics of [ 14 C]-Cefiderocol (S-649266), a Siderophore Cephalosporin, in Healthy Subjects Following Intravenous Administration

J Clin Pharmacol. 2019 Jul;59(7):958-967. doi: 10.1002/jcph.1386. Epub 2019 Feb 7.


The objectives of this study were to characterize the concentration-time profiles of total radioactivity equivalent and unchanged cefiderocol, the route(s) of elimination and mass balance, and safety of cefiderocol after intravenous administration of a single 1000-mg (100 μCi) dose of [14 C]-cefiderocol as a 1-hour infusion in healthy adult male subjects. Unchanged cefiderocol accounted for the majority of total radioactivity in plasma, and the partitioning of total radioactivity into red blood cells was negligible. The recovery of total radioactivity was complete in all subjects within 120 hours after initiation of the infusion (101.5% of the administered dose). Cefiderocol-related material was primarily excreted into urine, with 98.7% of the administered dose of [14 C]-cefiderocol excreted as total radioactivity into urine and negligible excretion into feces. Based on the results of metabolite profiling, cefiderocol accounted for 92.3% of area under the concentration-time curve of total radioactivity in plasma and accounted for 90.6% of the administered dose excreted into urine. Metabolism was a minor route of elimination for cefiderocol. Cefiderocol was generally safe and well tolerated in healthy adult male subjects. In conclusion, unchanged cefiderocol represents the majority of total radioactivity in plasma. Cefiderocol is primarily excreted as unchanged drug into urine. This study indicates that cefiderocol and drug-related material did not remain in the body.

Keywords: cefiderocol; cephalosporin; mass balance; metabolite profiling; pharmacokinetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Adult
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacokinetics*
  • Area Under Curve
  • Cephalosporins / administration & dosage
  • Cephalosporins / chemistry
  • Cephalosporins / pharmacokinetics*
  • Feces / chemistry
  • Half-Life
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Molecular Structure


  • Anti-Bacterial Agents
  • Cephalosporins
  • cefiderocol