title: Pharmacokinetics of eribulin mesylate in cancer patients with normal and impaired renal function.
abstract: OBJECTIVE
  To evaluate the effect of renal impairment on eribulin mesylate pharmacokinetics following a single dose in adults with advanced solid tumors.
  
  
  METHODS
  Patients were grouped by renal function: moderate impairment (creatinine clearance [CrCl] 30-50 mL/min), severe impairment (CrCl 15-29 mL/min), or normal (CrCl ≥80 mL/min). During each 21-day cycle, eribulin mesylate doses (days 1 and 8) were administered intravenously: moderate, 1.1 mg/m(2) (except cycle 1 day 1, 1.4 mg/m(2)); severe, 0.7 mg/m(2); normal, 1.4 mg/m(2).
  
  
  RESULTS
  Nineteen patients were enrolled (normal, n = 6; moderate, n = 7; severe, n = 6). Renal impairment was associated with an increased mean dose-normalized area under the concentration-time curve (ratios for moderate/normal and severe/normal: 1.49; 90 % confidence interval [CI] 0.9, 2.45). CrCl and renal function correlated positively, with a numerically small slope (0.0184; 90 % CI -0.00254, 0.0394). A simulated dose reduction to eribulin 1.1 mg/m(2) in patients with moderate or severe renal impairment achieved the same exposure as 1.4 mg/m(2) in those with normal renal function. All groups had similar toxicity profiles, with no unexpected adverse events.
  
  
  CONCLUSIONS
  Renal impairment decreased eribulin clearance and increased exposure. Pharmacokinetic evaluation supports an eribulin dose reduction to 1.1 mg/m(2) in patients with moderate or severe renal impairment. CLINICALTRIALS.
  NCT01418677.
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.|Department of Medical Oncology, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, 28204, USA.
authors.forename: Antoinette R
authors.initials: AR
authors.lastname: Tan
authors.affiliation: Institute for Drug Development, Cancer Therapy and Research Center, University of Texas Health Science Center San Antonio, San Antonio, TX, 78229, USA.
authors.forename: John
authors.initials: J
authors.lastname: Sarantopoulos
authors.affiliation: Department of Clinical Pharmacology and Translational Medicine, Eisai Inc., Woodcliff Lake, NJ, 07677, USA.
authors.forename: Lucy
authors.initials: L
authors.lastname: Lee
authors.affiliation: Department of Clinical Pharmacology and Translational Medicine, Oncology, Eisai Inc., Woodcliff Lake, NJ, 07677, USA.
authors.forename: Larisa
authors.initials: L
authors.lastname: Reyderman
authors.affiliation: Department of Biostatistics, Oncology, Eisai Inc., Woodcliff Lake, NJ, 07677, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Oncology Clinical Development, Eisai Inc., Woodcliff Lake, NJ, 07677, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Olivo
authors.affiliation: Department of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, 1695 Eastchester Road, Bronx, NY, 10461, USA. sgoel@montefiore.org.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Goel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000505:Alopecia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D003404:Creatinine / Q000097:blood; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005663:Furans / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D007659:Ketones / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007668:Kidney / Q000502:physiology*; D007674:Kidney Diseases / Q000503:physiopathology*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D016879:Salvage Therapy; D050257:Tubulin Modulators / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000095662:Polyether Polyketides
chemical_list: D000970:Antineoplastic Agents; D003404:Creatinine; D005663:Furans; D007659:Ketones; D050257:Tubulin Modulators; C490954:eribulin; D000095662:Polyether Polyketides
keywords: Cancer patients; Eribulin; Pharmacokinetics; Renal function; Renal impairment