| Item |
Information |
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Drug Groups
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approved; investigational |
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Description
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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 |
| • |
Humans and other mammals |
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| 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 |
| • |
Kansra S, Yamagata S, Sneade L, Foster L, Ben-Jonathan N: Differential effects of estrogen receptor antagonists on pituitary lactotroph proliferation and prolactin release. Mol Cell Endocrinol. 2005 Jul 15;239(1-2):27-36.
[Pubmed]
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| • |
Kabos P, Borges VF: Fulvestrant: a unique antiendocrine agent for estrogen-sensitive breast cancer. Expert Opin Pharmacother. 2010 Apr;11(5):807-16.
[Pubmed]
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| • |
Bross PF, Cohen MH, Williams GA, Pazdur R: FDA drug approval summaries: fulvestrant. Oncologist. 2002;7(6):477-80.
[Pubmed]
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| External Links |
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