Levels of fulvestrant with 500 mg/month by intramuscular injection (and a single additional 500 mg loading dose on day 15 of therapy) in postmenopausal women with advanced breast cancer were 25.1 ng/mL (25,100 pg/mL) at peak and 28.0 ng/mL (28,000 pg/mL) at trough with a single dose and 28.0 ng/mL (28,000 pg/mL) at peak and 12.2 ng/mL (12,200 pg/mL) at trough after multiple doses at steady state.Fulvestrant does not cross the blood–brain barrier in animals and may not in humans as well. Accordingly, no effects of fulvestrant on brain function have been observed in preclinical or clinical research. Fulvestrant is highly (99%) bound to plasma proteins. It is bound to very low density lipoprotein, low density lipoprotein, and high density lipoprotein, but not to sex hormone-binding globulin.Fulvestrant appears to be metabolized along similar pathways as endogenous steroids; CYP3A4 may be involved, but non-cytochrome P450 routes appear to be more important. It does not inhibit any cytochrome P450 enzymes. Elimination is almost all via feces.Fulvestrant can form colloidal aggregates at certain concentration ranges and this can limit its activity as well as produce bell-shaped concentration–response curves. Chemistry
Fulvestrant, also known as 7α-[9-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]estradiol, is a synthetic estrane steroid and a derivative of estradiol. An alkyl-sulfinyl moiety was added to the endogenous estrogen receptor ligand.It was discovered through rational drug design, but was selected for further development via phenotypic screening. History
Fulvestrant was the first selective estrogen receptor degrader to be approved. It was approved in the United States in 2002 and in Europe in 2004.
The clinical success of fulvestrant also led to efforts to discover and develop a parallel drug class of selective androgen receptor degraders (SARDs).ZB716, or fulvestrant-3-boronic acid, is an oral prodrug of fulvestrant which is under development. References
External links
"Fulvestrant". Drug Information Portal. U.S. National Library of Medicine.