Research
Clinical studies of raloxifene for metastatic breast cancer in women have been conducted but found little effectiveness at 60 mg/day in those previously treated with tamoxifen, though modest effectiveness has been observed at higher doses. In contrast to tamoxifen, raloxifene is not approved for the treatment of breast cancer.Raloxifene has been studied in men for a variety of uses, such as for treatment of schizophrenia, prostate cancer, and osteoporosis. It has been studied in combination with castration and bicalutamide, a nonsteroidal antiandrogen, for the treatment of prostate cancer.Raloxifene has been studied as an adjunct in the treatment of schizophrenia in postmenopausal women. A 2017 meta-analysis concluded that it was safe and effective for this indication, although further studies with larger sample sizes are needed for confirmation. It may be effective in women with less severe symptoms.A tissue-selective estrogen-receptor complex (TSEC) of estradiol and raloxifene has been studied in postmenopausal women.Raloxifene (60 mg/day) was reported to be effective in the treatment of pubertal gynecomastia in adolescent boys in a small retrospective chart review. Other SERMs are also known to be effective in the treatment of gynecomastia.Raloxifene has been reported to augment the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs).June 18th 2020, Exscalate4CoV, the private-public consortium supported by the EU’s Horizon 2020 programme for research and innovation, led by Dompé farmaceutici and currently representing 18 partners (including Fraunhofer Institute, CINECA, Chelonia Applied Science, Swiss Institute of Bioinformatics and others) has requested access to clinical trials for the use of Raloxifene in COVID-19 patients.
For these reasons, raloxifene increases the risk of thrombosis.Raloxifene increases bone mineral density in postmenopausal women but decreases it in premenopausal women. In the MORE trial, the risk of vertebral fractures was decreased by 30%, and bone mineral density was increased in the spine (by 2.1% at 60 mg, 2.4% at 120 mg) and femoral neck (2.6% at 60 mg, 2.7% at 120 mg). It has been found to possess estrogenic effects in adipose tissue in postmenopausal women, promoting a shift from an android fat distribution to a gynoid fat distribution. The medication has been found to increase levels of leptin, an adipokine. Pharmacokinetics
Absorption
The absorption of raloxifene is approximately 60%. However, due to extensive first-pass metabolism, the absolute bioavailability of raloxifene is only 2.0%. Raloxifene is rapidly absorbed from the intestines upon oral administration. Peak plasma levels of raloxifene occur 0.5 to 6 hours after an oral dose. In healthy postmenopausal women treated with 60 mg/day raloxifene, peak circulating raloxifene levels normalized by dose and body weight were (i.e., divided by (mg/kg)), 0.50 ng/mL (500 pg/mL) after a single dose and 1.36 ng/mL (1,360 pg/mL after multiple doses). Distribution
Raloxifene is widely distributed throughout the body. There is extensive distribution of raloxifene into the liver, serum, lungs, and kidneys. The volume of distribution of raloxifene with a single 30 to 150 mg oral dose is approximately 2348 L/kg, which corresponds to ~170,000 L for a 72 kg person.