Pharmacokinetics of selective estrogen receptor modulators

Karla C. Morello, Gregory T. Wurz, Michael W. DeGregorio

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

Selective estrogen receptor modulators (SERMs) are a class of compounds used to treat and prevent breast cancer and osteoporosis. SERMs currently approved for use in patients include tamoxifen, toremifene and raloxifene. These compounds are well tolerated in patients, and the most common adverse effects experienced in patients undergoing SERM therapy include vasomotor symptoms such as hot flashes and vaginal discharge. New SERMs currently under development for use in the treatment and prevention of osteoporosis and breast cancer include ospemifene, a derivative of toremifene, and arzoxifene, a compound very similar in structure to raloxifene. SERMs are administered orally at doses ranging from 20 to 60 mg/day. Tamoxifen and toremifene have a bioavailability of approximately 100%, whereas that of raloxifene is only 2%. SERMs are very highly bound to plasma proteins (>95%). Tamoxifen and toremifene are metabolised by the cytochrome P450 enzyme system, and raloxifene is metabolised by glucuronide conjugation. The terminal elimination half-lives of these drugs range from 27.7 hours to 7 days. The pharmacokinetics of these compounds are affected in hepatically impaired patients, but not in renally impaired patients. SERMs have several potential drug interactions with other agents, such as warfarin, rifampicin (rifampin), cholestyramine and aromatase inhibitors.

Original languageEnglish (US)
Pages (from-to)361-372
Number of pages12
JournalClinical Pharmacokinetics
Volume42
Issue number4
DOIs
StatePublished - 2003

Fingerprint

Selective Estrogen Receptor Modulators
Toremifene
Pharmacokinetics
Tamoxifen
LY 353381
Cytochrome P-450 Enzyme System
Osteoporosis
Hot Flashes
Breast Neoplasms
Cholestyramine Resin
Vaginal Discharge
Aromatase Inhibitors
Glucuronides
Warfarin
Rifampin
Drug Interactions
Biological Availability
Blood Proteins
Raloxifene Hydrochloride
Therapeutics

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Pharmacokinetics of selective estrogen receptor modulators. / Morello, Karla C.; Wurz, Gregory T.; DeGregorio, Michael W.

In: Clinical Pharmacokinetics, Vol. 42, No. 4, 2003, p. 361-372.

Research output: Contribution to journalArticle

Morello, Karla C. ; Wurz, Gregory T. ; DeGregorio, Michael W. / Pharmacokinetics of selective estrogen receptor modulators. In: Clinical Pharmacokinetics. 2003 ; Vol. 42, No. 4. pp. 361-372.
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