The effect of renal and hepatic impairment on the pharmacokinetics of ospemifene, a tissue-selective estrogen agonist/antagonist

Richard A Preston, Thomas C. Marbury, Toshihiro Wajima, Shelli Graham

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 (AUC 0-∞) and maximum concentration (C max), 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.

Original languageEnglish (US)
Pages (from-to)171-181
Number of pages11
JournalAmerican Journal of Therapeutics
Volume22
Issue number3
DOIs
StatePublished - May 16 2015

Fingerprint

Estrogen Antagonists
Pharmacokinetics
Confidence Intervals
Kidney
Liver
Dyspareunia
Ospemifene
Area Under Curve
Atrophy

Keywords

  • hepatic impairment
  • ospemifene
  • postmenopausal women
  • renal impairment

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

The effect of renal and hepatic impairment on the pharmacokinetics of ospemifene, a tissue-selective estrogen agonist/antagonist. / Preston, Richard A; Marbury, Thomas C.; Wajima, Toshihiro; Graham, Shelli.

In: American Journal of Therapeutics, Vol. 22, No. 3, 16.05.2015, p. 171-181.

Research output: Contribution to journalArticle

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