Formestane

DB08905

small molecule approved investigational withdrawn

Deskripsi

Formestane was the first selective, type I, steroidal aromatase inhibitor used in the treatment of estrogen-receptor positive breast cancer in post-menopausal women. Formestane suppresses estrogen production from anabolic steroids or prohormones. Formestane is also a prohormone of 4-hydroxytestosterone, an active steroid with weak androgenic activity and mild aromatase inhibitor activity. It is listed as a prohibited substance by the World Anti-Doping Agency for use in athletes.

Formestane has poor oral bioavailability, and thus must be administered fortnightly (bi-weekly) by intramuscular injection. Some clinical data has suggested that the clinically recommended dose of 250mg was too low. With the discovery of newer, non-steroidal and steroidal, aromatase inhibitors which were orally active and less expensive than formestane, formestane lost popularity.

Currently, formestane (categorized as an anti-estrogenic agent) is prohibited from use in sports in accordance to the regulations of the World Anti-Doping Agency. It is not US FDA approved, and the intramuscular injection form of formestane (Lentaron) which was approved in Europe has been withdrawn.

Struktur Molekul 2D

Berat 302.4079
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) Terminal plasma elimination half life of 18 minutes, when delivered intravenously.[A14440]
Volume Distribusi Vd = 1.8 L/kg; widely distributed to organs and tissues when delivered intravenously.[A14440]
Klirens (Clearance) Plasma clearance is approximately 4.2 L/(h kg), when delivered intravenously. In women, following a 500mg dose of formestane, 20% was excreted as glucuronide within the first 24 hours. [1] One long term metabolite (3beta,4alpha-dihydroxy-5alpha-androstan-17-one) can be detected for 90 hours. A longer detection time is possible with more sensitive technology, which may be of utility in sports drug testing. [1]

Absorpsi

Formestane has poor oral bioavailability, but is fully bioavailable when administered via the established intramuscular route. The AUC after an intravenous pulse dose does not vary considerably from that of an intramuscular dose. Within 24-48 h of the first dose of intramuscular formestane, a C(max) of 48.0 +/- 20.9 nmol/l was achieved in one study.A14440

Metabolisme

Hepatic metabolism. Phase I of metabolism is mainly reductive in nature. The reduction products 3 beta-hydroxy-5alpha-androstane-4,17-dione and 3alpha-hydroxy-5beta-androstane-4,17-dione are produced, and further reduced. A notable step in the process of metabolism is a keto reduction on carbon number three of the molecule. The main metabolite which is produced from formestane is 4-hydroyxyandrost-4-ene-3,17-dione-4-glucuronide. The oxidation products identified were 4-hydroxyandrosta-4,6-diene-3,17-dione and 4-hydroxyandrosta-1,4-diene-3,17-dione. In phase II, conjugation was diverse and included sulfatation and glucuronidation. 4-hydroxytestosterone, the 17-hydroxylated analog to formestane, was identified as one particular metabolite found in women's urine. This finding was the result of an oral administration of 500mg of formestane in women.

Rute Eliminasi

Renal elimination. >95% in urine, <5% in feces.

Interaksi Obat

993 Data
Aripiprazole The metabolism of Aripiprazole can be increased when combined with Formestane.
Aripiprazole lauroxil The metabolism of Aripiprazole lauroxil can be increased when combined with Formestane.
Ifosfamide The metabolism of Ifosfamide can be increased when combined with Formestane.
Perampanel The metabolism of Perampanel can be increased when combined with Formestane.
Warfarin The metabolism of Warfarin can be increased when combined with Formestane.
Acenocoumarol The metabolism of Acenocoumarol can be increased when combined with Formestane.
(R)-warfarin The metabolism of (R)-warfarin can be increased when combined with Formestane.
R,S-Warfarin alcohol The metabolism of R,S-Warfarin alcohol can be increased when combined with Formestane.
S,R-Warfarin alcohol The metabolism of S,R-Warfarin alcohol can be increased when combined with Formestane.
(S)-Warfarin The metabolism of (S)-Warfarin can be increased when combined with Formestane.
Methadone The serum concentration of Methadone can be increased when it is combined with Formestane.
Erlotinib The serum concentration of Erlotinib can be decreased when it is combined with Formestane.
Flunisolide The risk or severity of edema formation can be increased when Formestane is combined with Flunisolide.
Beclomethasone dipropionate The risk or severity of edema formation can be increased when Formestane is combined with Beclomethasone dipropionate.
Betamethasone The risk or severity of edema formation can be increased when Formestane is combined with Betamethasone.
Fluticasone propionate The risk or severity of edema formation can be increased when Formestane is combined with Fluticasone propionate.
Fluocinolone acetonide The risk or severity of edema formation can be increased when Formestane is combined with Fluocinolone acetonide.
Triamcinolone The risk or severity of edema formation can be increased when Formestane is combined with Triamcinolone.
Prednisone The risk or severity of edema formation can be increased when Formestane is combined with Prednisone.
Fludrocortisone The risk or severity of edema formation can be increased when Formestane is combined with Fludrocortisone.
Hydrocortisone The risk or severity of edema formation can be increased when Formestane is combined with Hydrocortisone.
Prednisolone The risk or severity of edema formation can be increased when Formestane is combined with Prednisolone.
Methylprednisolone The risk or severity of edema formation can be increased when Formestane is combined with Methylprednisolone.
Trilostane The risk or severity of edema formation can be increased when Formestane is combined with Trilostane.
Dexamethasone The risk or severity of edema formation can be increased when Formestane is combined with Dexamethasone.
Corticotropin The risk or severity of edema formation can be increased when Formestane is combined with Corticotropin.
Cortisone acetate The risk or severity of edema formation can be increased when Formestane is combined with Cortisone acetate.
Paramethasone The risk or severity of edema formation can be increased when Formestane is combined with Paramethasone.
Ciclesonide The risk or severity of edema formation can be increased when Formestane is combined with Ciclesonide.
Aldosterone The risk or severity of edema formation can be increased when Formestane is combined with Aldosterone.
Fluticasone furoate The risk or severity of edema formation can be increased when Formestane is combined with Fluticasone furoate.
Fluprednidene The risk or severity of edema formation can be increased when Formestane is combined with Fluprednidene.
Tixocortol The risk or severity of edema formation can be increased when Formestane is combined with Tixocortol.
Fluprednisolone The risk or severity of edema formation can be increased when Formestane is combined with Fluprednisolone.
Meprednisone The risk or severity of edema formation can be increased when Formestane is combined with Meprednisone.
Dexamethasone isonicotinate The risk or severity of edema formation can be increased when Formestane is combined with Dexamethasone isonicotinate.
Melengestrol The risk or severity of edema formation can be increased when Formestane is combined with Melengestrol.
Deflazacort The risk or severity of edema formation can be increased when Formestane is combined with Deflazacort.
Cortivazol The risk or severity of edema formation can be increased when Formestane is combined with Cortivazol.
Prednylidene The risk or severity of edema formation can be increased when Formestane is combined with Prednylidene.
Fluocortin The risk or severity of edema formation can be increased when Formestane is combined with Fluocortin.
Fluperolone The risk or severity of edema formation can be increased when Formestane is combined with Fluperolone.
Cloprednol The risk or severity of edema formation can be increased when Formestane is combined with Cloprednol.
Fluclorolone The risk or severity of edema formation can be increased when Formestane is combined with Fluclorolone.
Fluticasone The risk or severity of edema formation can be increased when Formestane is combined with Fluticasone.
Mometasone furoate The risk or severity of edema formation can be increased when Formestane is combined with Mometasone furoate.
Hydrocortisone acetate The risk or severity of edema formation can be increased when Formestane is combined with Hydrocortisone acetate.
Hydrocortisone cypionate The risk or severity of edema formation can be increased when Formestane is combined with Hydrocortisone cypionate.
Hydrocortisone succinate The risk or severity of edema formation can be increased when Formestane is combined with Hydrocortisone succinate.
Prednisolone phosphate The risk or severity of edema formation can be increased when Formestane is combined with Prednisolone phosphate.
Prednisolone hemisuccinate The risk or severity of edema formation can be increased when Formestane is combined with Prednisolone hemisuccinate.
Methylprednisolone hemisuccinate The risk or severity of edema formation can be increased when Formestane is combined with Methylprednisolone hemisuccinate.
Prednisone acetate The risk or severity of edema formation can be increased when Formestane is combined with Prednisone acetate.
Clocortolone acetate The risk or severity of edema formation can be increased when Formestane is combined with Clocortolone acetate.
Melengestrol acetate The risk or severity of edema formation can be increased when Formestane is combined with Melengestrol acetate.
Betamethasone phosphate The risk or severity of edema formation can be increased when Formestane is combined with Betamethasone phosphate.
Cortisone The risk or severity of edema formation can be increased when Formestane is combined with Cortisone.
Budesonide The risk or severity of edema formation can be increased when Formestane is combined with Budesonide.
Clobetasol propionate The risk or severity of edema formation can be increased when Formestane is combined with Clobetasol propionate.
Fluocinonide The risk or severity of edema formation can be increased when Formestane is combined with Fluocinonide.
Hydrocortisone butyrate The risk or severity of edema formation can be increased when Formestane is combined with Hydrocortisone butyrate.
Desoximetasone The risk or severity of edema formation can be increased when Formestane is combined with Desoximetasone.
Mometasone The risk or severity of edema formation can be increased when Formestane is combined with Mometasone.
Fluocortolone The risk or severity of edema formation can be increased when Formestane is combined with Fluocortolone.
Prednisolone acetate The risk or severity of edema formation can be increased when Formestane is combined with Prednisolone acetate.
Fluorometholone The risk or severity of edema formation can be increased when Formestane is combined with Fluorometholone.
Difluocortolone The risk or severity of edema formation can be increased when Formestane is combined with Difluocortolone.
Flumethasone The risk or severity of edema formation can be increased when Formestane is combined with Flumethasone.
Methylprednisolone aceponate The risk or severity of edema formation can be increased when Formestane is combined with Methylprednisolone aceponate.
Segesterone acetate The metabolism of Segesterone acetate can be increased when combined with Formestane.
Icosapent Icosapent may decrease the excretion rate of Formestane which could result in a higher serum level.
Cefotiam Cefotiam may decrease the excretion rate of Formestane which could result in a higher serum level.
Mesalazine Mesalazine may decrease the excretion rate of Formestane which could result in a higher serum level.
Cefmenoxime Cefmenoxime may decrease the excretion rate of Formestane which could result in a higher serum level.
Cefmetazole Cefmetazole may decrease the excretion rate of Formestane which could result in a higher serum level.
Pamidronic acid Pamidronic acid may decrease the excretion rate of Formestane which could result in a higher serum level.
Tenofovir disoproxil Tenofovir disoproxil may decrease the excretion rate of Formestane which could result in a higher serum level.
Indomethacin Indomethacin may decrease the excretion rate of Formestane which could result in a higher serum level.
Cidofovir Cidofovir may decrease the excretion rate of Formestane which could result in a higher serum level.
Cefpiramide Cefpiramide may decrease the excretion rate of Formestane which could result in a higher serum level.
Ceftazidime Ceftazidime may decrease the excretion rate of Formestane which could result in a higher serum level.
Loracarbef Loracarbef may decrease the excretion rate of Formestane which could result in a higher serum level.
Cefalotin Cefalotin may decrease the excretion rate of Formestane which could result in a higher serum level.
Nabumetone Nabumetone may decrease the excretion rate of Formestane which could result in a higher serum level.
Ketorolac Ketorolac may decrease the excretion rate of Formestane which could result in a higher serum level.
Tenoxicam Tenoxicam may decrease the excretion rate of Formestane which could result in a higher serum level.
Celecoxib Celecoxib may decrease the excretion rate of Formestane which could result in a higher serum level.
Cefotaxime Cefotaxime may decrease the excretion rate of Formestane which could result in a higher serum level.
Tolmetin Tolmetin may decrease the excretion rate of Formestane which could result in a higher serum level.
Foscarnet Foscarnet may decrease the excretion rate of Formestane which could result in a higher serum level.
Rofecoxib Rofecoxib may decrease the excretion rate of Formestane which could result in a higher serum level.
Piroxicam Piroxicam may decrease the excretion rate of Formestane which could result in a higher serum level.
Fenoprofen Fenoprofen may decrease the excretion rate of Formestane which could result in a higher serum level.
Valaciclovir Valaciclovir may decrease the excretion rate of Formestane which could result in a higher serum level.
Valdecoxib Valdecoxib may decrease the excretion rate of Formestane which could result in a higher serum level.
Diclofenac Diclofenac may decrease the excretion rate of Formestane which could result in a higher serum level.
Sulindac Sulindac may decrease the excretion rate of Formestane which could result in a higher serum level.
Bacitracin Bacitracin may decrease the excretion rate of Formestane which could result in a higher serum level.
Amphotericin B Amphotericin B may decrease the excretion rate of Formestane which could result in a higher serum level.
Cephaloglycin Cephaloglycin may decrease the excretion rate of Formestane which could result in a higher serum level.

Target Protein

Aromatase CYP19A1

Referensi & Sumber

Synthesis reference: Kohler, Maxie, et al. "Metabolism of 4-hydroxyandrostenedione and 4-hydroxytestosterone: Mass spectrometric identification of urinary metabolites." Steroids 72.3 (2007): 278-286.
Artikel (PubMed)
  • PMID: 7873457
    Perez Carrion R, Alberola Candel V, Calabresi F, Michel RT, Santos R, Delozier T, Goss P, Mauriac L, Feuilhade F, Freue M, et al.: Comparison of the selective aromatase inhibitor formestane with tamoxifen as first-line hormonal therapy in postmenopausal women with advanced breast cancer. Ann Oncol. 1994;5 Suppl 7:S19-24.
  • PMID: 17207827
    Kohler M, Parr MK, Opfermann G, Thevis M, Schlorer N, Marner FJ, Schanzer W: Metabolism of 4-hydroxyandrostenedione and 4-hydroxytestosterone: Mass spectrometric identification of urinary metabolites. Steroids. 2007 Mar;72(3):278-86. Epub 2007 Jan 17.
  • PMID: 11358673
    Lonning PE, Geisler J, Johannessen DC, Gschwind HP, Waldmeier F, Schneider W, Galli B, Winkler T, Blum W, Kriemler HP, Miller WR, Faigle JW: Pharmacokinetics and metabolism of formestane in breast cancer patients. J Steroid Biochem Mol Biol. 2001 Apr;77(1):39-47.
  • PMID: 7873455
    Murray R, Pitt P: Treatment of advanced breast cancer with formestane. Ann Oncol. 1994;5 Suppl 7:S11-3.
  • PMID: 10586340
    Vorobiof DA, Kleeberg UR, Perez-Carrion R, Dodwell DJ, Robertson JF, Calvo L, Dowsett M, Clack G: A randomized, open, parallel-group trial to compare the endocrine effects of oral anastrozole (Arimidex) with intramuscular formestane in postmenopausal women with advanced breast cancer. Ann Oncol. 1999 Oct;10(10):1219-25.

Contoh Produk & Brand

Produk: 1 • International brands: 0
Produk
  • Lentaron
    Liquid; Powder, for solution • - • Intramuscular • Canada • Approved

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