Drug Groups

approved; investigational

Description

Fulvestrant is a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor.

Indication

For the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy.

Pharmacology

Fulvestrant for intramuscular administration is an estrogen receptor antagonist without known agonist effects.

Toxicity

There is no clinical experience with overdosage in humans.

Affected Organisms

Biotransformation

Metabolism of fulvestrant appears to involve combinations of a number of possible biotransformation pathways analogous to those of endogenous steroids, including oxidation, aromatic hydroxylation, conjugation with glucuronic acid and/or sulphate at the 2, 3 and 17 positions of the steroid nucleus, and oxidation of the side chain sulphoxide. Identified metabolites are either less active or exhibit similar activity to fulvestrant in antiestrogen models. Studies using human liver preparations and recombinant human enzymes indicate that cytochrome P-450 3A4 (CYP 3A4) is the only P-450 isoenzyme involved in the oxidation of fulvestrant; however, the relative contribution of P-450 and non-P-450 routes in vivo is unknown.

Half Life

40 days

Protein Binding

99% (mainly VLDL, LDL, and HDL)

Elimination

Fulvestrant was rapidly cleared by the hepatobiliary route with excretion primarily via the feces (approximately 90%).
Renal elimination was negligible (less than 1%).

Distribution

* 3 to 5 L/kg

References

External Links