title: Pharmacokinetics of eplerenone after single and multiple dosing in subjects with and without renal impairment.
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.
authors.affiliation: Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Ravis
authors.forename: Susan
authors.initials: S
authors.lastname: Reid
authors.forename: Domenic A
authors.initials: DA
authors.lastname: Sica
authors.forename: Dwain S
authors.initials: DS
authors.lastname: Tolbert
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D003404:Creatinine / Q000378:metabolism; D000077545:Eplerenone; D005260:Female; D006801:Humans; D006947:Hyperkalemia / Q000209:etiology; D007674:Kidney Diseases / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists; D006435:Renal Dialysis; D013148:Spironolactone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone; D003404:Creatinine