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Mass balance study of [¹⁴C]eribulin in patients with advanced solid tumors.

Abstract
This mass balance study investigated the metabolism and excretion of eribulin, a nontaxane microtubule dynamics inhibitor with a novel mechanism of action, in patients with advanced solid tumors. A single approximately 2 mg (approximately 80 μCi) dose of [¹⁴C]eribulin acetate was administered as a 2 to 5 min bolus injection to six patients on day 1. Blood, urine, and fecal samples were collected at specified time points on days 1 to 8 or until sample radioactivity was ≤1% of the administered dose. Mean plasma eribulin exposure (627 ng · h/ml) was comparable with that of total radioactivity (568 ng Eq · h/ml). Time-matched concentration ratios of eribulin to total radioactivity approached unity in blood and plasma, indicating that unchanged parent compound constituted almost all of the eribulin-derived radioactivity. Only minor metabolites were detected in plasma samples up to 60 min postdose, pooled across patients, each metabolite representing ≤0.6% of eribulin. Elimination half-lives for eribulin (45.6 h) and total radioactivity (42.3 h) were comparable. Eribulin-derived radioactivity excreted in feces was 81.5%, and that of unchanged eribulin was 61.9%. Renal clearance (0.301 l/h) was a minor component of total eribulin clearance (3.93 l/h). Eribulin-derived radioactivity excreted in urine (8.9%) was comparable with that of unchanged eribulin (8.1%), indicating minimal excretion of metabolite(s) in urine. Total recovery of the radioactive dose was 90.4% in urine and feces. Overall, no major metabolites of eribulin were detected in plasma. Eribulin is eliminated primarily unchanged in feces, whereas urine constitutes a minor route of elimination.
AuthorsAnne-Charlotte Dubbelman, Hilde Rosing, Robert S Jansen, Marja Mergui-Roelvink, Alwin D R Huitema, Barbara Koetz, Margarita Lymboura, Larisa Reyderman, Arturo Lopez-Anaya, Jan H M Schellens, Jos H Beijnen
JournalDrug metabolism and disposition: the biological fate of chemicals (Drug Metab Dispos) Vol. 40 Issue 2 Pg. 313-21 (Feb 2012) ISSN: 1521-009X [Electronic] United States
PMID22041109 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Carbon Radioisotopes
  • Furans
  • Ketones
  • Tubulin Modulators
  • eribulin
Topics
  • Adult
  • Aged
  • Antineoplastic Agents (analysis, blood, pharmacokinetics, urine)
  • Biotransformation
  • Carbon Radioisotopes
  • Feces (chemistry)
  • Female
  • Furans (analysis, blood, pharmacokinetics, urine)
  • Half-Life
  • Humans
  • Ketones (analysis, blood, pharmacokinetics, urine)
  • Male
  • Metabolic Clearance Rate
  • Microtubules (metabolism)
  • Middle Aged
  • Neoplasms (metabolism)
  • Tubulin Modulators (analysis, blood, pharmacokinetics, urine)

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