Ambrisentan

{{Drugbox

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| verifiedrevid = 437179007

| image = Ambrisentan structure.svg

| width = 200

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| tradename = Letairis, Volibris, Pulmonext

| Drugs.com = {{drugs.com|monograph|ambrisentan}}

| MedlinePlus = a612023

| DailyMedID = Ambrisentan

| pregnancy_AU = X

| pregnancy_category =

| routes_of_administration = By mouth

| ATC_prefix = C02

| ATC_suffix = KX02

| legal_AU = S4

| legal_AU_comment = {{cite web | title=Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | access-date=30 March 2024}}

| legal_CA = Rx-only

| legal_UK = POM

| legal_US = Rx-only

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| legal_EU = Rx-only

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| legal_status = Rx-only

| bioavailability =

| protein_bound = 99%

| metabolism =

| elimination_half-life = 15 hours (terminal)

| excretion =

| IUPHAR_ligand = 3951

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 177036-94-1

| PubChem = 6918493

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB06403

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| ChemSpiderID = 5293690

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| UNII = HW6NV07QEC

| KEGG_Ref =

| KEGG = D07077

| ChEBI_Ref =

| ChEBI = 135949

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 1111

| IUPAC_name = (2S)-2-[(4,6-dimethylpyrimidin-2-yl)oxy]-3-methoxy-3,3-diphenylpropanoic acid

| C=22 | H=22 | N=2 | O=4

| smiles = O=C(O)[C@@H](Oc1nc(cc(n1)C)C)C(OC)(c2ccccc2)c3ccccc3

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| StdInChI = 1S/C22H22N2O4/c1-15-14-16(2)24-21(23-15)28-19(20(25)26)22(27-3,17-10-6-4-7-11-17)18-12-8-5-9-13-18/h4-14,19H,1-3H3,(H,25,26)/t19-/m1/s1

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

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Ambrisentan, sold under the brand name Letairis among others, is a drug used for the treatment of pulmonary hypertension.{{cite web | title=Letairis- ambrisentan tablet, film coated | website=DailyMed | date=4 September 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=725d4e73-6c83-477a-adc6-0ae4a133a844 | access-date=18 April 2020}}{{cite web | title=Ambrisentan Monograph for Professionals | website=Drugs.com | publisher=American Society of Health-System Pharmacists | date=7 January 2019 | url=https://www.drugs.com/monograph/ambrisentan.html | access-date=18 April 2020}} It is an endothelin receptor antagonist.

The peptide endothelin constricts muscles in blood vessels, increasing blood pressure. Ambrisentan, which relaxes those muscles, is an endothelin receptor antagonist, and is selective for the type A endothelin receptor (ET_A).{{cite journal | vauthors = Vatter H, Seifert V | title = Ambrisentan, a non-peptide endothelin receptor antagonist | journal = Cardiovascular Drug Reviews | volume = 24 | issue = 1 | pages = 63–76 | year = 2006 | pmid = 16939634 | doi = 10.1111/j.1527-3466.2006.00063.x | doi-access = free }} Ambrisentan significantly improved exercise capacity (6-minute walk distance) compared with placebo in two double-blind, multicenter trials (ARIES-1 and ARIES-2).{{cite journal | vauthors = Frampton JE | title = Ambrisentan | journal = American Journal of Cardiovascular Drugs | volume = 11 | issue = 4 | pages = 215–26 | date = August 2011 | pmid = 21623643 | doi = 10.2165/11207340-000000000-00000 | s2cid = 262016778 }} Like all endothelin receptor antagonists, Ambrisentan is contraindicated in pregnant women as well as those who are trying to become pregnant, due to the potential for teratogenic effects on the fetus.{{cite journal | vauthors = Galiè N, Olschewski H, Oudiz RJ, Torres F, Frost A, Ghofrani HA, Badesch DB, McGoon MD, McLaughlin VV, Roecker EB, Gerber MJ, Dufton C, Wiens BL, Rubin LJ | display-authors = 6 | title = Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2 | journal = Circulation | volume = 117 | issue = 23 | pages = 3010–9 | date = June 2008 | pmid = 18506008 | doi = 10.1161/CIRCULATIONAHA.107.742510 | doi-access = free }}

Ambrisentan was approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), and designated an orphan drug, for the treatment of pulmonary hypertension.{{cite web | title=Drug Approval Package: Letairis (ambrisentan) NDA #022081 | website=U.S. Food and Drug Administration (FDA) | date=24 December 1999 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000TOC.cfm | access-date=18 April 2020}}{{cite web | title=Volibris EPAR | website=European Medicines Agency (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/volibris | access-date=18 April 2020}}{{cite web | title=Ambrisentan Orphan Drug Designation and Approval | website=U.S. Food and Drug Administration (FDA) | url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=183604 | access-date=18 April 2020}}{{cite news | vauthors = Pollack A | title = Gilead's Drug Is Approved to Treat a Rare Disease | work = The New York Times | date = 16 June 2007 | url = https://www.nytimes.com/2007/06/16/business/16gilead.html | access-date = 16 June 2007 | archive-url = https://web.archive.org/web/20130524115948/http://www.nytimes.com/2007/06/16/business/16gilead.html| archive-date = May 24, 2013| url-status = live}}

Medical uses

Ambrisentan is indicated for the treatment of pulmonary arterial hypertension (WHO Group 1) in people with WHO class II or III symptoms to improve exercise capacity and delay clinical worsening.

Mechanism of action

Ambrisentan is a drug that blocks endothelin, an endogenous hormone found in higher quantities in patients with pulmonary arterial hypertension. Endothelin binds to two receptors, ET_A and ET_B. ET_A is responsible for cell growth in the vessels as well as vasoconstriction, while ET_B plays a role in vasodilation, endothelin 1 clearance, and antiproliferation of cells.

Birth defects

Endothelin receptor activation mediates strong pulmonary vasoconstriction and positive inotropic effect on the heart. These physiologic effects are vital for the development of the fetal cardiopulmonary (heart and lung) system. In addition to this, endothelin receptors are also known to play a role in neural crest cell migration, growth, and differentiation. As such, endothelin receptor antagonists such as ambrisentan are known to be teratogenic.

Society and culture

= Brand names =

Ambrisentan is sold under the brand name Letairis, Volibris, and Pulmonext.{{cn|date=December 2023}}

Publications

class="wikitable"
colspan="2" \| Last updated 9/2/2015
8/15/2015 Reprod. Toxicol.	Endothelin receptor activation mediates strong pulmonary vasoconstriction and positive inotropic effect on the heart. These physiologic effects are vital for the development of the fetal cardiopulmonary system. As such, endothelin receptor antagonists such as ambrisentan are teratogenic.{{cite journal \|vauthors=de Raaf MA, Beekhuijzen M, Guignabert C, Vonk Noordegraaf A, Bogaard HJ \|title=Endothelin-1 receptor antagonists in fetal development and pulmonary arterial hypertension \|journal=Reproductive Toxicology \|volume=56 \|pages=45–51 \|year=2015 \|pmid=26111581 \|doi=10.1016/j.reprotox.2015.06.048 \|bibcode=2015RepTx..56...45D }}
8/27/2015 NEJM	Ambrisentan when used in combination therapy with tadalafil was found to be more efficacious in treating treatment naive patients with WHO class II or III pulmonary arterial hypertension than monotherapy using either drug.{{cite journal \| vauthors = Galiè N, Barberà JA, Frost AE, Ghofrani HA, Hoeper MM, McLaughlin VV, Peacock AJ, Simonneau G, Vachiery JL, Grünig E, Oudiz RJ, Vonk-Noordegraaf A, White RJ, Blair C, Gillies H, Miller KL, Harris JH, Langley J, Rubin LJ \| display-authors = 6 \| title = Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension \| journal = The New England Journal of Medicine \| volume = 373 \| issue = 9 \| pages = 834–44 \| date = August 2015 \| pmid = 26308684 \| doi = 10.1056/NEJMoa1413687 \| doi-access = free \| hdl = 2445/97236 \| hdl-access = free }}

class="wikitable"

colspan="2" |

Last updated 9/2/2015

8/15/2015 Reprod. Toxicol.

Endothelin receptor activation mediates strong pulmonary vasoconstriction and positive inotropic effect on the heart. These physiologic effects are vital for the development of the fetal cardiopulmonary system. As such, endothelin receptor antagonists such as ambrisentan are teratogenic.{{cite journal |vauthors=de Raaf MA, Beekhuijzen M, Guignabert C, Vonk Noordegraaf A, Bogaard HJ |title=Endothelin-1 receptor antagonists in fetal development and pulmonary arterial hypertension |journal=Reproductive Toxicology |volume=56 |pages=45–51 |year=2015 |pmid=26111581 |doi=10.1016/j.reprotox.2015.06.048 |bibcode=2015RepTx..56...45D }}

8/27/2015 NEJM

Ambrisentan when used in combination therapy with tadalafil was found to be more efficacious in treating treatment naive patients with WHO class II or III pulmonary arterial hypertension than monotherapy using either drug.{{cite journal | vauthors = Galiè N, Barberà JA, Frost AE, Ghofrani HA, Hoeper MM, McLaughlin VV, Peacock AJ, Simonneau G, Vachiery JL, Grünig E, Oudiz RJ, Vonk-Noordegraaf A, White RJ, Blair C, Gillies H, Miller KL, Harris JH, Langley J, Rubin LJ | display-authors = 6 | title = Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension | journal = The New England Journal of Medicine | volume = 373 | issue = 9 | pages = 834–44 | date = August 2015 | pmid = 26308684 | doi = 10.1056/NEJMoa1413687 | doi-access = free | hdl = 2445/97236 | hdl-access = free }}

References

Category:Endothelin receptor antagonists

Category:Diphenylmethanol ethers

Category:Gilead Sciences

Category:Orphan drugs

Category:Pyrimidines

Category:Acetic acids