title: The effect of renal and hepatic impairment on the pharmacokinetics of ospemifene, a tissue-selective estrogen agonist/antagonist.
abstract: Ospemifene is a nonestrogen tissue-selective estrogen agonist/antagonist approved to treat moderate to severe dyspareunia due to vulvar and vaginal atrophy in postmenopausal women. Three single-dose, open-label, parallel-group pharmacokinetic studies examined the pharmacokinetics of ospemifene in postmenopausal women with (1) mild hepatic impairment (n = 7), (2) moderate hepatic impairment (n = 8), and (3) severe renal impairment (n = 8) compared with a similar number of matched healthy controls. The study durations ranged from 8 to 12 days. Study participants received a single oral dose of ospemifene 60 mg on day 1 and blood samples were collected serially. The geometric mean ratios (hepatic or renal impairment/healthy) and 90% confidence intervals (CIs) for area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-∞) and maximum concentration (Cmax), respectively, of ospemifene were 90.86% (90% CI, 65.95%-125.19%) and 79.48% (90% CI, 65.95%-95.79%) in the mild hepatic impairment study; 128.62% (90% CI, 87.13%-189.88%) and 101.12% (90% CI, 66.17%-154.52%) in the moderate hepatic impairment study, and 119.63% (90% CI, 81.37%-175.88%) and 79.30% (90% CI, 52.85%-118.99%) in the severe renal impairment study. Overall, there was no clinically important effect of hepatic or renal impairment on the pharmacokinetics of ospemifene, indicating that dosing does not need to be adjusted in postmenopausal women with mild or moderate hepatic impairment or in subjects with severe renal impairment.
authors.affiliation: 1Division of Clinical Pharmacology, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL; 2Jackson Memorial Hospital, Miami, FL; 3Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL; 4Orlando Clinical Research Center, Orlando, FL; 5Clinical Pharmacology & Pharmacokinetics, Clinical Research Department, Shionogi & Co., Ltd, Osaka, Japan; and 6Shionogi Inc., Florham Park, NJ.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Preston
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Marbury
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Wajima
authors.forename: Shelli
authors.initials: S
authors.lastname: Graham
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D004967:Estrogens / Q000378:metabolism; D005260:Female; D048550:Hepatic Insufficiency / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D051437:Renal Insufficiency / Q000378:metabolism*; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects / Q000493:pharmacokinetics*; D013629:Tamoxifen / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D004967:Estrogens; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; C119141:Ospemifene