Ospemifene might not have an adverse influence on coagulation, in contrast to estrogens and other SERMs like tamoxifen and raloxifene.A binding assay was also performed to measure the affinity of ospemifene for the estrogen receptor (ERα and ERβ). The study showed that ospemifene bound ERα and ERβ with similar affinity. Ospemifene bound the estrogen receptors with a lower affinity than estradiol. Ospemifene was shown to be an antagonist of "ERE-mediated transactivation on MCF-7 cells," which the authors concluded indicates "anti-estrogenic activity in breast cancer cells." Pharmacokinetics
The pharmacokinetics of ospemifene were dose-dependent over a dose range of 10 to 800 mg/day. History
Approval process
Hormos Medical Ltd., which is a part of QuatRx Pharmaceuticals, filed a patent on January 19, 2005, for a solid dosage form of ospemifene. In March 2010, QuatRX Pharmaceuticals licensed ospemifene to Shionogi & Co., Ltd. for clinical development and marketing. A New Drug Application (NDA) was submitted to the FDA on April 26, 2012. Amendments to the NDA were submitted in June, July, August, October, and November 2012, and January and February 2013. It was ultimately approved by the FDA on February 26, 2013. Ospemifene (under the brand name Senshio) was subsequently approved by the European Commission for marketing in the EU in January 2015. Preclinial and clinical trials
Preclinical trials were performed in ovariectomized rats to model menopause. Oral ospemifene was compared with raloxifene (another SERM), its metabolites 4-hydroxy ospemifene and 4-hydroxy ospemifene, estradiol, and ospemifene administered as an intravaginal suppository.
Management
Differentiation of DIOS from constipation is generally performed by unit specializing in the treatment of cystic fibrosis. Adequate hydration and an aggressive regimen of laxatives are essential for treatment and prevention of DIOS. Osmotic laxatives such as polyethylene glycol are preferred. Individuals prone to DIOS tend to be at risk for repeated episodes and often require maintenance therapy with pancreatic enzyme replacement, hydration and laxatives (if the symptoms are also mild). Oral contrast instillation into the colon/ileum under radiological control has been found to reduce the need for surgical intervention. References
External links
http://www.cfmedicine.com/htmldocs/CFText/dios.htm
http://www.rbht.nhs.uk/healthprofessionals/clinical-departments/cystic-fibrosis/clinical-guidelines/nutritional-and-gastrointestinal-care/constipation-and-distal-intestinal-obstructive-syndrome/