Absorption, Distribution and Excretion
Formestan has low oral bioavailability, but complete bioavailability when administered via the established intramuscular route. The AUC after an intravenous pulse dose is not significantly different from that after an intramuscular dose. One study showed that the peak plasma concentration (Cmax) reached 48.0 ± 20.9 nmol/L within 24–48 hours after the first intramuscular injection of formestan. [2]
Renal excretion. >95% is excreted in urine and <5% in feces.
Volume of distribution (Vd) = 1.8 L/kg; widely distributed in organs and tissues after intravenous administration. [2]
Plasma clearance after intravenous administration is approximately 4.2 L/(h·kg). 20% of women who take 500 mg of formestan are excreted as glucuronide within 24 hours. [1] A long-acting metabolite (3β,4α-dihydroxy-5α-androstan-17-one) can be detected within 90 hours. More sensitive techniques can enable longer detection times, which may be helpful for the detection of sports drugs. [1]

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Metabolism/Metabolites
Hepatic metabolism. The first stage of metabolism is mainly a reduction reaction. The reduction products 3β-hydroxy-5α-androstane-4,17-dione and 3α-hydroxy-5β-androstane-4,17-dione are generated and further reduced. A noteworthy step in the metabolism is the reduction of the ketone on the third carbon of the molecule. The major metabolite of formestan is 4-hydroxyandrostane-4-ene-3,17-dione-4-glucuronide. The oxidation products identified are 4-hydroxyandrostane-4,6-diene-3,17-dione and 4-hydroxyandrostane-1,4-diene-3,17-dione. In phase II, the binding reactions are diverse, including sulfation and glucuronidation. 4-Hydroxytestosterone is a 17-hydroxylated analog of formestan, identified as a specific metabolite found in the urine of women. This discovery was based on oral administration of 500 mg formestan to women.

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Biological half-life
The terminal plasma elimination half-life after intravenous administration is 18 minutes. [2]

Steroids.2013Nov;78(11):1103-9;Ann Oncol.1994;5 Suppl 7:S19-24.

Formestane is a 17-oxosteroid with the structure androst-4-en-3,17-dione, where the hydrogen at the 4-position is replaced by a hydroxyl group. Formestan was the first selective type I steroid aromatase inhibitor, inhibiting the production of estrogen from anabolic steroids or prohormones. It was previously used to treat estrogen receptor-positive breast cancer in postmenopausal women. Due to its low oral bioavailability, it had to be administered via intramuscular injection (every two weeks). With the advent of cheaper, orally effective aromatase inhibitors, formestan was gradually phased out. The World Anti-Doping Agency has listed formestan as a prohibited substance for athletes. It is an EC 1.14.14.14 (aromatase) inhibitor and an anti-tumor drug. It is a 3-oxo-Δ⁴ steroid, a 17-oxosteroid, a hydroxysteroid, and an enol. It is derived from the hydrogenation of androstane. Formestan is the first selective type I steroid aromatase inhibitor used to treat estrogen receptor-positive breast cancer in postmenopausal women. Formestan inhibits the production of estrogen by anabolic steroids or pro-estrogens. It is also a pro-estrogen of 4-hydroxytestosterone, an active steroid with weak androgenic activity and mild aromatase inhibitory activity. The World Anti-Doping Agency (WADA) has listed it as a prohibited substance for athletes. Formestan has low oral bioavailability, therefore it must be administered intramuscularly every two weeks. Some clinical data suggest that the recommended clinical dose of 250 mg is too low. With the discovery of new non-steroidal and steroid aromatase inhibitors that are effective orally and cheaper than formestan, formestan has gradually lost market share. Currently, according to WADA regulations, formestan (classified as an anti-estrogenic drug) is prohibited for use in sports. It has not been approved by the U.S. Food and Drug Administration (FDA), and the intramuscular form of formestan (Lentaron), which was previously approved in Europe, has also been withdrawn from the market. Formestan is a synthetic steroid with antitumor activity. Formestan irreversibly binds to and inhibits aromatase activity, thereby blocking the conversion of cholesterol to pregnenolone and the peripheral conversion of androgen precursors to estrogen. (NCI04)
See also: 4-hydroxytestosterone (note moved here).
Indications: For the treatment of estrogen receptor-positive breast cancer in postmenopausal women.
Mechanism of Action: Formestan is a second-generation irreversible steroid aromatase inhibitor. It inhibits aromatase, the enzyme responsible for converting androgens to estrogens, thus preventing estrogen production. Breast cancer may be estrogen-sensitive or estrogen-insensitive. Most breast cancers are estrogen-sensitive. Estrogen-sensitive breast cancer cells depend on estrogen to survive. Therefore, removing estrogen from the body can effectively treat hormone-sensitive breast cancer. Formestan is specifically used to treat postmenopausal women. Unlike premenopausal women, who have the highest estrogen levels in their ovaries, postmenopausal women have the highest estrogen levels in their peripheral tissues with the help of aromatase. Formestane is an aromatase inhibitor that can treat hormone-sensitive breast cancer by blocking aromatase in peripheral tissues (such as breast adipose tissue) and reducing local estrogen production.

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Pharmacodynamics
Formestane may exert antitumor activity by significantly reducing estrogen levels in the blood. In a trial involving 147 postmenopausal women with advanced breast cancer resistant to standard therapy, 22% of patients achieved partial remission and another 20% had stable disease. [3] In a comparative trial of the nonsteroidal aromatase inhibitors anastrozole and formestane, anastrozole was found to be more effective and more stable in suppressing estrogen levels in the body. However, the clinical significance of these results has not been confirmed. [5]

C19H26O3

302.41

302.188

566-48-3

11273

Typically exists as solid at room temperature

1.2±0.1 g/cm3

475.4±45.0 °C at 760 mmHg

199-202°C

255.4±25.2 °C

0.0±2.7 mmHg at 25°C

1.570

2.66

1

3

0

22

590

5

C[C@@]12CCC(=O)C(=C2CC[C@H]3[C@@H]4CCC(=O)[C@@]4(C)CC[C@@H]31)O

OSVMTWJCGUFAOD-KZQROQTASA-N

InChI=1S/C19H26O3/c1-18-10-8-15(20)17(22)14(18)4-3-11-12-5-6-16(21)19(12,2)9-7-13(11)18/h11-13,22H,3-10H2,1-2H3/t11-,12-,13-,18+,19-/m0/s1

(8R,9S,10R,13S,14S)-4-hydroxy-10,13-dimethyl-7,8,9,10,11,12,13,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17(2H,6H)-dione

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)