Estramustine

From Infogalactic: the planetary knowledge core
Jump to: navigation, search
Estramustine
Skeletal formula of estramustine
Ball-and-stick model of the estramustine molecule
Systematic (IUPAC) name
(17β)-17-Hydroxyestra-1(10),2,4-trien-3-yl bis(2-chloroethyl)carbamate
Clinical data
Trade names Emcyt
AHFS/Drugs.com monograph
MedlinePlus a608046
Licence data US FDA:link
Pregnancy
category
  • AU: D
  • US: X (Contraindicated)
Legal status
Pharmacokinetic data
Bioavailability 75%[1]
Metabolism Hepatic to estradiol and estrone[1]
Biological half-life 15-24 hours[1]
Excretion Faeces (2.9-4.8%)[1]
Identifiers
CAS Number 2998-57-4 YesY
ATC code L01XX11 (WHO)
PubChem CID: 259331
DrugBank DB01196 YesY
ChemSpider 227635 YesY
UNII 35LT29625A YesY
KEGG D04066 YesY
ChEBI CHEBI:4868 YesY
ChEMBL CHEMBL1575 YesY
Chemical data
Formula C23H31Cl2NO3
Molecular mass 440.403 g/mol
  • ClCCN(C(=O)Oc1cc3c(cc1)[C@H]2CC[C@@]4([C@@H](O)CC[C@H]4[C@@H]2CC3)C)CCCl
  • InChI=1S/C23H31Cl2NO3/c1-23-9-8-18-17-5-3-16(29-22(28)26(12-10-24)13-11-25)14-15(17)2-4-19(18)20(23)6-7-21(23)27/h3,5,14,18-21,27H,2,4,6-13H2,1H3/t18-,19-,20+,21+,23+/m1/s1 YesY
  • Key:FRPJXPJMRWBBIH-RBRWEJTLSA-N YesY
  (verify)

Estramustine (Emcyt, Estracit) is an antimicrotubule chemotherapy agent used to treat prostate cancer. It is a derivative of oestrogen (specifically, estradiol) with a nitrogen mustard-carbamate ester moiety. It has been withdrawn from a number of markets (Australia, Brazil, Ireland and Norway).[2]

Clinical uses

Estramustine is indicated, in the US, for the palliative treatment of metastatic and/or progressive prostate cancer.[1] Whereas in the UK it is indicated for the treatment of unresponsive or relapsing prostate cancer.[3][4][5][6]

Adverse effects

Adverse effects by frequency:[1][3]
Very common (>10% frequency):

<templatestyles src="Div col/styles.css"/>

  • Oedema
  • Dyspnoea
  • Nausea
  • Diarrhoea
  • Breast tenderness and enlargement

Common (1-10% frequency):

<templatestyles src="Div col/styles.css"/>

Rare (<0.1% frequency):

<templatestyles src="Div col/styles.css"/>

  • Angiooedema, occurs most commonly when used in combination with ACE inhibitors.

Unlike other nitrogen mustards it seldom produces significant GI or haematologic toxicity such as myelosuppression,[4] the major drug toxicity-related cause of drug discontinuation is thromboembolism (blood clots).[7]

Contraindications

It is contraindicated when used in children, patients hypersensitive to estradiol or nitrogen mustards, those with peptic ulcer (an ulcer in the digestive tract), those with severely compromised liver function, those with weak heart muscle (also known as myocardial insufficiency) and those with thromboembolic disorders or complications related to fluid retention.[3]

Interactions

Oestrogen mimics like estramustine have been reported to increase the toxicity and therapeutic efficacy of tricyclic antidepressants like amitriptyline and imipramine.[3] Dairy products and other products containing calcium, aluminium and magnesium have been reported to reduce the absorption of estramustine from the gastrointestinal tract hence reducing bioavailability.[3] There may be an increased risk of angiooedema in those concurrently taking ACE inhibitors.[3]

Mechanism of action

Its therapeutic actions are believed to be related to its ability to depolymerising the microtubules (which it achieves by binding to microtubule associated proteins), this arrests prostate cancer cells in the G2/M phase of the cell cycle.[4][5][6] It is selectively taken up by prostate cells and hence produces minimal cytotoxic effects on healthy tissue.[4]

Pharmacokinetics

Estramustine is delivered as an oral capsule. It is readily taken up from the gastrointestinal tract and then rapidly dephosphorylated from estramustine phosphate to estramustine.[4] Estramustine is then partially oxidised to estromustine.[4] Some estramustine and estromustine undergoes hydrolysis at the ester bond in the liver to form estradiol, estrone and normustine.[4] Milk, calcium, aluminium and magnesium supplements may reduce bioavailability.[3]

Active metabolites of estramustine
Estramustine Estromustine Estradiol Estrone Normustine
Estramustine2DACS.svg
Estromustine2DACS.svg
Oestradiol2DACS.svg
Oestrone2DACS.svg
Normustine2DACS.svg

See also

References

<templatestyles src="Reflist/styles.css" />

Cite error: Invalid <references> tag; parameter "group" is allowed only.

Use <references />, or <references group="..." />

External links


  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ 5.0 5.1 Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ 6.0 6.1 Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
Retrieved from "https://infogalactic.com/w/index.php?title=Estramustine&oldid=4714653"