Pharmacokinetics of Selective Estrogen Receptor Modulators

  title={Pharmacokinetics of Selective Estrogen Receptor Modulators},
  author={Karla C. Morello and Gregory T. Wurz and Michael W. DeGregorio},
  journal={Clinical Pharmacokinetics},
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… 
Selective estrogen receptor modulator (SERM) for the treatment of osteoporosis in postmenopausal women: focus on lasofoxifene
Lasofoxifene, a new-generation SERM that has completed phase III development for the prevention and treatment of osteoporosis in postmenopausal women, is reviewed, showing increased efficacy on the prevention of nonvertebral fractures than current available SERMs and its positive effects on the vagina.
Ospemifene use in postmenopausal women
The recently released results from a pivotal Phase III study in postmenopausal women demonstrated statistically significant improvements of ospemifene 60 mg/day in symptoms of vulvar and vaginal atrophy over the use of non-hormonal vaginal lubricant.
Lasofoxifene, a new selective estrogen receptor modulator for the treatment of osteoporosis and vaginal atrophy
  • L. Gennari
  • Medicine, Biology
    Expert opinion on pharmacotherapy
  • 2009
With its increased potency and efficacy on the prevention of nonvertebral fractures and its positive effects on the vagina, this new SERM may represent an alternative therapy for osteoporosis in postmenopausal women.
Lasofoxifene: Selective Estrogen Receptor Modulator for the Prevention and Treatment of Postmenopausal Osteoporosis
While the results of further clinical trials are needed to define the risks and benefits of treatment, particularly relating to fractures, lasofoxifene may prove to be an effective and well-tolerated therapeutic option for the prevention of bone toss in postmenopausal women.
Lasofoxifene: a third-generation selective estrogen receptor modulator for the prevention and treatment of osteoporosis
Lasofoxifene has a remarkably improved oral bioavailability with respect to other SERMs due to increased resistance to intestinal wall glucuronidation and demonstrated a proven efficacy in preventing bone loss and lowering cholesterol levels.
Clinical Pharmacology of Lasofoxifene in Japanese and White Postmenopausal Women
Lasofoxifene has a potency at estrogen receptors that is at least equal to that of estradiol in preventing bone loss and inhibiting bone turnover in ovariectomized rats, and it may be related to its high estrogen receptor alpha (ERα) affinity.
Disposition of Lasofoxifene, a Next-Generation Selective Estrogen Receptor Modulator, in Healthy Male Subjects
The results from in vitro experiments with recombinant isoforms and P450 isoform-selective inhibitors suggested that the oxidative metabolism of lasofoxifene is catalyzed primarily by CYP3A and CYP2D6.
Lasofoxifene, from the preclinical drug discovery to the treatment of postmenopausal osteoporosis
Lasofoxifene, a new SERM for the treatment of postmenopausal osteoporosis and urogenital atrophy, may offer an improved skeletal efficacy over raloxifenes, addressing other post menopausal conditions, including reduction in breast cancer risk and treatment of vaginal atrophy.
Pilot Study Evaluating the Pharmacokinetics, Pharmacodynamics, and Safety of the Combination of Exemestane and Tamoxifen
Evidence is provided that coadministration of tamoxifen does not affect exemestane pharmacokinetics or pharmacodynamics and that the combination is well-tolerated and active.
Raloxifene: Promises and Challenges as a Drug Treatment for Castrate Resistant Prostate Cancer
Raloxifene, a SERM, approved for the treatment of osteoporosis in post-menopausal women, exhibits potent anti-cancer activity in in vitro and in vivo models of CRPC, but poor bioavailability, extensive metabolism, and poor water solubility have reduced its efficacy in animal studies and clinical trials.


Raloxifene: A selective estrogen receptor modulator (SERM) with multiple target system effects.
The preclinical and clinical pharmacology of raloxifene is explored, and it is compared to other SERMs currently available for clinical use to improve the drug safety profile.
Pharmacokinetics of raloxifene and its clinical application.
  • D. Hochner-Celnikier
  • Medicine, Biology
    European journal of obstetrics, gynecology, and reproductive biology
  • 1999
Tamoxifen and toremifene in breast cancer: comparison of safety and efficacy.
  • A. BuzdarG. Hortobagyi
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 1998
Toremifene is not likely to be used as second-line therapy after tamoxifen failure due to cross-resistance, and its ultimate place in therapy of advanced breast cancer remains to be determined.
Raloxifene: a selective estrogen receptor modulator.
Raloxifene is a selective estrogen receptor modulator that produces both estrogen-agonistic effects on bone and lipid metabolism and estrogen-antagonistic effects on uterine endometrium and breast
Clinical Pharmacokinetics of Toremifene
The pharmacokinetics of toremifene have been shown to be altered by certain liver conditions, but age and kidney function do not appear to be as significant.
Toremifene. A review of its pharmacological properties and clinical efficacy in the management of advanced breast cancer.
Toremifene provides an equally effective and well tolerated alternative to tamoxifen for the first-line endocrine therapy of postmenopausal advanced breast cancer.
Phase I study of the tolerance and pharmacokinetics of toremifene in patients with cancer
The most common side-effects associated with therapy included gastrointestinal, anti-estrogenic, and CNS (dizziness/vertigo 12%).
Phase I clinical and pharmacokinetics study of high-dose toremifene in postmenopausal patients with advanced breast cancer
A total of 19 previously treated postmenopausal women with metastatic breast cancer whose performance status was good and whose ER status was positive or unknown were studied to determine the maximum tolerated dose of toremifene, an antiestrogen that binds strongly to estrogen receptors (ER).
Biochemical and pharmacological effects of toremifene metabolites
  • L. Kangas
  • Biology, Chemistry
    Cancer Chemotherapy and Pharmacology
  • 2004
Toremifene, a new antiestrogenic antitumor compound, has several biologically active metabolites, including N-demethylated metabolites to (deamino)hydroxylated compounds and carboxylic acids, which have pharmacological properties similar to those of toremifene.
Effects of raloxifene on serum lipids and coagulation factors in healthy postmenopausal women.
Raloxifene favorably alters biochemical markers of cardiovascular risk by decreasing LDL-C, fibrinogen, and lipoprotein(a), and by increasing HDL2-C without raising triglycerides.