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Ambrisentan
Clinical data
Trade namesLetairis, Volibris, Pulmonext
AHFS/Drugs.comMonograph
MedlinePlusa612023
License data
Pregnancy
category
  • AU: X (High risk)
Routes of
administration
By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding99%
Elimination half-life15 hours (terminal)
Identifiers
  • (2S)-2-[(4,6-dimethylpyrimidin-2-yl)oxy]-3-methoxy-3,3-diphenylpropanoic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.184.855 Edit this at Wikidata
Chemical and physical data
FormulaC22H22N2O4
Molar mass378.428 g·mol−1
3D model (JSmol)
  • O=C(O)[C@@H](Oc1nc(cc(n1)C)C)C(OC)(c2ccccc2)c3ccccc3
  • InChI=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 checkY
  • Key:OUJTZYPIHDYQMC-LJQANCHMSA-N checkY
  (verify)

Ambrisentan, sold under the brand name Letairis among others, is a drug used for the treatment of pulmonary hypertension.[2][4] It is an endothelin receptor antagonist.[2]

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 (ETA).[5] Ambrisentan significantly improved exercise capacity (6-minute walk distance) compared with placebo in two double-blind, multicenter trials (ARIES-1 and ARIES-2).[6] 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.[7]

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.[8][3][9][10]

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.[2][3]

Mechanism of action

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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, ETA and ETB. ETA is responsible for cell growth in the vessels as well as vasoconstriction, while ETB plays a role in vasodilation, endothelin 1 clearance, and antiproliferation of cells.

Birth defects

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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. 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,[2] Volibris,[3] and Pulmonext.[citation needed]

Publications

This section needs to be updated. Please help update this article to reflect recent events or newly available information. (April 2020)

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.[11]
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.[12]

References

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  2. ^ a b c d e "Letairis- ambrisentan tablet, film coated". DailyMed. 4 September 2019. Retrieved 18 April 2020.
  3. ^ a b c d "Volibris EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 18 April 2020.
  4. ^ "Ambrisentan Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. 7 January 2019. Retrieved 18 April 2020.
  5. ^ Vatter H, Seifert V (2006). "Ambrisentan, a non-peptide endothelin receptor antagonist". Cardiovascular Drug Reviews. 24 (1): 63–76. doi:10.1111/j.1527-3466.2006.00063.x. PMID 16939634.
  6. ^ Frampton JE (August 2011). "Ambrisentan". American Journal of Cardiovascular Drugs. 11 (4): 215–26. doi:10.2165/11207340-000000000-00000. PMID 21623643. S2CID 262016778.
  7. ^ Galiè N, Olschewski H, Oudiz RJ, Torres F, Frost A, Ghofrani HA, et al. (June 2008). "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". Circulation. 117 (23): 3010–9. doi:10.1161/CIRCULATIONAHA.107.742510. PMID 18506008.
  8. ^ "Drug Approval Package: Letairis (ambrisentan) NDA #022081". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 18 April 2020.
  9. ^ "Ambrisentan Orphan Drug Designation and Approval". U.S. Food and Drug Administration (FDA). Retrieved 18 April 2020.
  10. ^ Pollack A (16 June 2007). "Gilead's Drug Is Approved to Treat a Rare Disease". The New York Times. Archived from the original on 24 May 2013. Retrieved 16 June 2007.
  11. ^ de Raaf MA, Beekhuijzen M, Guignabert C, Vonk Noordegraaf A, Bogaard HJ (2015). "Endothelin-1 receptor antagonists in fetal development and pulmonary arterial hypertension". Reproductive Toxicology. 56: 45–51. doi:10.1016/j.reprotox.2015.06.048. PMID 26111581.
  12. ^ Galiè N, Barberà JA, Frost AE, Ghofrani HA, Hoeper MM, McLaughlin VV, et al. (August 2015). "Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension". The New England Journal of Medicine. 373 (9): 834–44. doi:10.1056/NEJMoa1413687. hdl:2445/97236. PMID 26308684.