Abstract
This mass balance study investigated the metabolism and excretion of eribulin, a non-taxane microtubule dynamics inhibitor with a novel mechanism of action, in patients with advanced solid tumours. A single ~2 mg (~80 μCi) dose of 14C-eribulin acetate was administered as a 2–5 min bolus injection to 6 patients on day 1. Blood, urine, and faecal samples were collected at specified time points on days 1-8 or until sample radioactivity was ≤1% of the administered dose. Mean plasma eribulin exposure (627 ng.h/mL) was comparable to 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 eribulin-derived radioactivity. Only minor metabolites were detected in plasma samples up to 60 min post-dose, 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 faeces 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 was comparable (8.9%) to 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 faeces. Overall, no major metabolites of eribulin were detected in plasma. Eribulin is primarily eliminated unchanged in faeces, while urine constitutes a minor route of elimination.
- Received October 3, 2011.
- Accepted October 26, 2011.
- The American Society for Pharmacology and Experimental Therapeutics