title: 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.
authors: Department of Clinical Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. anne-charlotte.dubbelman@slz.nl
authors: Anne-Charlotte
authors: AC
authors: Dubbelman
authors: Hilde
authors: H
authors: Rosing
authors: Robert S
authors: RS
authors: Jansen
authors: Marja
authors: M
authors: Mergui-Roelvink
authors: Alwin D R
authors: AD
authors: Huitema
authors: Barbara
authors: B
authors: Koetz
authors: Margarita
authors: M
authors: Lymboura
authors: Larisa
authors: L
authors: Reyderman
authors: Arturo
authors: A
authors: Lopez-Anaya
authors: Jan H M
authors: JH
authors: Schellens
authors: Jos H
authors: JH
authors: Beijnen
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001711:Biotransformation; D002250:Carbon Radioisotopes; D005243:Feces / Q000737:chemistry; D005260:Female; D005663:Furans / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006207:Half-Life; D006801:Humans; D007659:Ketones / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D008657:Metabolic Clearance Rate; D008870:Microtubules / Q000378:metabolism; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism*; D050257:Tubulin Modulators / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000095662:Polyether Polyketides
chemical_list: D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D005663:Furans; D007659:Ketones; D050257:Tubulin Modulators; C490954:eribulin; D000095662:Polyether Polyketides