The main representatives of the selective estrogen receptor modulators or SERMs - are Tamoxifen (Nolvadex), Clomiphene (Clomid), Raloxifene (Evista), Toremifene (Fareston), as well as more recent, little studied analogues of tamoxifen (idoxifen, keoxifen, droloxifene). All of these SERM drugs class are in their structure non-steroidal substances. Fulvestrant belongs to steroid representatives of SERMs class.
Tamoxifen
The first antiestrogen from SERM class, tamoxifen, was synthesized by the CoIe group in 1971, and its active use as an estrogen receptor blocker began. In the last decade, a highly selective "pure" steroid blocker of estrogen receptor fulvestrant has been created, which is currently undergoing stage III clinical trials.
The most commonly used drug in pharmacology for SERM class is tamoxifen, a competitive inhibitor of peripheral estrogen receptors. Currently, the point of view indicating that tamoxifen does not have an estrogen-like effect has been disproved, since it is proved that this drug also exhibits estrogenic activity to a certain extent - the ratio of its agonistic and antagonistic activity is 45/55.
Tamoxifen is a derivative of triphenylethylene; chemical structure of 1- [p- (2-dimethylamino) ethoxy] phenyl-trans-1,2-diphenyl-1-butene, in the form of citrate. Release form: tablets on 10, 20, and 40 mg. Tamoxifen is well absorbed in the stomach; the first peak of its concentration in the blood plasma is recorded 1-6 hours after administration, and the second - after 24-44 hours. This drug circulates in the blood for a rather long time - up to a maximum of 170 hours.
The elimination of tamoxifen is protracted and biphasic. The initial half-life of this drug is 24–53 hours, and the final, depending on the dose, from 3 to 18 days. Withdrawal of this drug occurs mainly through the gastrointestinal tract, and about 85-90% of the metabolized drug is excreted with feces and bile; a small part of it is excreted from the body by kidneys.
Tamoxifen is excreted from the body almost exclusively in the form of metabolites. The main biotransformation products are represented by glucuronide and other conjugates, as well as indefinite polar metabolites. The primary stage of biotransformation of the drug is hydroxylation of the aromatic ring to form a monohydroxy derivative.
