Metabolism and disposition of the anticancer quinolone derivative vosaroxin, a novel inhibitor of topoisomerase II

Invest New Drugs. 2017 Aug;35(4):478-490. doi: 10.1007/s10637-017-0428-1. Epub 2017 Jan 31.


Background Vosaroxin is a first-in-class anticancer quinolone derivative that is being investigated for patients with relapsed or refractory acute myeloid leukemia (AML). The primary objective of this study was to quantitatively determine the pharmacokinetics of vosaroxin and its metabolites in patients with advanced solid tumors. Methods This mass balance study investigated the pharmacokinetics (distribution, metabolism, and excretion) of vosaroxin in cancer patients after a single dose of 60 mg/m2 14C-vosaroxin, administered as short intravenous injection. Blood, urine and feces were collected over 168 h after injection or until recovered radioactivity over 24 h was less than 1% of the administered dose (whichever was earlier). Total radioactivity (TRA), vosaroxin and metabolites were studied in all matrices. Results Unchanged vosaroxin was the major species identified in plasma, urine, and feces. N-desmethylvosaroxin was the only circulating metabolite detected in plasma, accounting for <3% of the administered dose. However, in plasma, the combined vosaroxin + N-desmethylvosaroxin AUC0-∞ was 21% lower than the TRA AUC0-∞ , suggesting the possible formation of protein bound metabolites after 48 h when the concentration-time profiles diverged. The mean recovery of TRA in excreta was 81.3% of the total administered dose; 53.1% was excreted through feces and 28.2% through urine. Conclusions Unchanged vosaroxin was the major compound found in the excreta, although 10 minor metabolites were detected. The biotransformation reactions were demethylation, hydrogenation, decarboxylation and phase II conjugation including glucuronidation.

Keywords: ADME; Anti-cancer; Mass balance; Metabolite profiling; Pharmacokinetics; Vosaroxin.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Biotransformation
  • Carbon Radioisotopes
  • Feces / chemistry
  • Female
  • Humans
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Naphthyridines / adverse effects
  • Naphthyridines / blood
  • Naphthyridines / pharmacokinetics*
  • Naphthyridines / urine
  • Neoplasms / blood
  • Neoplasms / metabolism*
  • Neoplasms / urine
  • Thiazoles / adverse effects
  • Thiazoles / blood
  • Thiazoles / pharmacokinetics*
  • Thiazoles / urine
  • Topoisomerase II Inhibitors / adverse effects
  • Topoisomerase II Inhibitors / blood
  • Topoisomerase II Inhibitors / pharmacokinetics*
  • Topoisomerase II Inhibitors / urine


  • Carbon Radioisotopes
  • Naphthyridines
  • Thiazoles
  • Topoisomerase II Inhibitors
  • vosaroxin