Pharmacokinetics of eplerenone after single and multiple dosing in subjects with and without renal impairment

J Clin Pharmacol. 2005 Jul;45(7):810-21. doi: 10.1177/0091270005275894.

Abstract

The influence of renal impairment on the pharmacokinetics of eplerenone following single and multiple dosing was evaluated. Subjects (n = 64) were stratified based on creatinine clearance values as follows: renal impairment (mild, moderate, severe), hemodialysis, and normal matches. Subjects received a single dose of eplerenone 100 mg on day 1 and then received 100 mg once daily on days 3 to 8. There were no statistically significant differences between any of the renal impairment groups and their matched-normal groups for area under the curve (AUC), C(max), or CL/F or CL/F/WT following either single or multiple dosing (P > or = .093). The inactive metabolite and inactive ring-opened form displayed greater AUCs in renal impairment. Hemodialysis removed approximately 10% of the eplerenone dose. Eplerenone 100 mg once daily was well tolerated in all groups. Considering that renal function had no significant effects on eplerenone CL/F and that eplerenone metabolites are inactive, no dose adjustment appears necessary in patients with renal dysfunction.

Publication types

  • Clinical Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Area Under Curve
  • Creatinine / metabolism
  • Eplerenone
  • Female
  • Humans
  • Hyperkalemia / etiology
  • Kidney Diseases / metabolism*
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists
  • Renal Dialysis
  • Spironolactone / administration & dosage
  • Spironolactone / adverse effects
  • Spironolactone / analogs & derivatives*
  • Spironolactone / blood
  • Spironolactone / pharmacokinetics
  • Spironolactone / urine

Substances

  • Mineralocorticoid Receptor Antagonists
  • Spironolactone
  • Eplerenone
  • Creatinine