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Ambrisentan (U.S. trade name Letairis; E.U. trade name Volibris; India trade name pulmonext by MSN labs ) is a drug indicated for use in the treatment of pulmonary hypertension.

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

Ambrisentan was approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency, and designated an orphan drug, for the treatment of pulmonary hypertension.^[3]^[4]^[5]^[6]^[7]

Recent Developments and Publications

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.^[8]
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.^[9]

Clinical uses

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

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 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.

Abrisentan has a high risk of liver damage, and of birth defects if a woman becomes pregnant while taking it. In the U.S., doctors who prescribe it, and patients who take it, must enroll in a special program, the LETAIRIS Education and Access Program (LEAP), to learn about those risks. Abrisentan is only available through specialty pharmacies.

External links

Letairis website run by Gilead Sciences
Prescribing information^{[dead link]}
Information on the LETAIRIS Education and Access Program (LEAP)^{[dead link]}

References

^ Vatter H, Seifert V (2006). "Ambrisentan, a non-peptide endothelin receptor antagonist". Cardiovasc Drug Rev 24 (1): 63–76. doi:10.1111/j.1527-3466.2006.00063.x. PMID 16939634.
^ Frampton JE (2011). "Ambrisentan". American Journal of Cardiovascular Drugs 11 (4): 215–26. doi:10.2165/11207340-000000000-00000. PMID 21623643.
^ Pollack, Andrew (2007-06-16). "Gilead’s Drug Is Approved to Treat a Rare Disease". New York Times. Archived from the original on 20 June 2007. Retrieved 2007-05-25.
^ "U.S. Food and Drug Administration Approves Gilead's Letairis Treatment of Pulmonary Arterial Hypertension" (Press release). Gilead Sciences. 2007-06-15. Retrieved 2007-06-16.
^ "FDA Approves New Orphan Drug for Treatment of Pulmonary Arterial Hypertension" (Press release). Food and Drug Administration. 2007-06-15. Archived from the original on 23 June 2007. Retrieved 2007-06-22.
^ "GlaxoSmithKline's Volibris (ambrisentan) receives authorisation from the European Commission for the treatment of Functional Class II and III Pulmonary Arterial Hypertension" (Press release). GlaxoSmithKline. 2008-04-25. Archived from the original on 30 April 2008. Retrieved 2008-04-29.
^ Waknine, Yael (2005-05-09). "International Approvals: Ambrisentan, Oral-lyn, Risperdal". Medscape. Retrieved 2007-06-16.
^ 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.
^ Galiè, Nazzareno; Barberà, Joan A.; Frost, Adaani E.; Ghofrani, Hossein-Ardeschir; Hoeper, Marius M.; McLaughlin, Vallerie V.; Peacock, Andrew J.; Simonneau, Gérald; Vachiery, Jean-Luc; Grünig, Ekkehard; Oudiz, Ronald J.; Vonk-Noordegraaf, Anton; White, R. James; Blair, Christiana; Gillies, Hunter; Miller, Karen L.; Harris, Julia H.N.; Langley, Jonathan; Rubin, Lewis J. (2015). "Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension". New England Journal of Medicine 373 (9): 834–44. doi:10.1056/NEJMoa1413687.

UpToDate Contents

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English Journal

Oral vasodilator therapy in patients with moderate to severe portopulmonary hypertension as a bridge to liver transplantation.

Raevens S, De Pauw M, Reyntjens K, Geerts A, Verhelst X, Berrevoet F, Rogiers X, Troisi RI, Van Vlierberghe H, Colle I.SourceaDepartments of Hepatology and Gastroenterology bCardiology cAnesthesiology dGeneral and Hepatobiliary Surgery, Liver Transplantation Service, Ghent University Hospital, Ghent, Belgium.
European journal of gastroenterology & hepatology.Eur J Gastroenterol Hepatol.2012 Dec 13. [Epub ahead of print]
Portopulmonary hypertension (POPH) is a part of group 1 pulmonary hypertension (pulmonary hypertension associated with portal hypertension). Liver transplantation (LTx) may be curative, but is usually restricted to patients with mild-to-moderate POPH. The presence of severe POPH may be a contraindic
PMID 23242127

Influence of sildenafil and tadalafil on the enzyme- and transporter-inducing effects of bosentan and ambrisentan in LS180 cells.

Weiss J, Theile D, Spalwisz A, Burhenne J, Riedel KD, Haefeli WE.SourceDepartment of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Electronic address: johanna.weiss@med.uni-heidelberg.de.
Biochemical pharmacology.Biochem Pharmacol.2012 Dec 4. pii: S0006-2952(12)00761-7. doi: 10.1016/j.bcp.2012.11.020. [Epub ahead of print]
The combinations of the endothelin-1 receptor antagonists bosentan or ambrisentan with the phosphodiesterase 5 inhibitors sildenafil or tadalafil are current standard therapies of advanced pulmonary arterial hypertension. However, these drugs have a number of drug interactions. Changes of bosentan p
PMID 23219525

Japanese Journal

エンドセリン受容体拮抗薬 (特集肺高血圧症--基礎と臨床の最前線) -- (新たな治療法の今後の展開)

江本憲昭
綜合臨床 58(11), 2307-2312, 2009-11
NAID 40016883916

「アンブリセンタン」

Ambrisentan
Systematic (IUPAC) name
	(2S)-2-[(4,6-dimethylpyrimidin-2-yl)oxy]-3-methoxy- 3,3-diphenylpropanoic acid
Clinical data
AHFS/Drugs.com	monograph
Licence data	EMA:Link, US FDA:link
Pregnancy; category	AU: X (High risk); US: X (Contraindicated); ;
Legal status	AU: S4 (Prescription only); CA: ℞-only; UK: POM (Prescription only); US: ℞-only;
Routes of; administration	Oral
Pharmacokinetic data
Bioavailability	Undetermined
Protein binding	99%
Biological half-life	15 hours (terminal)
Identifiers
CAS Number	177036-94-1
ATC code	C02KX02
PubChem	CID: 6918493
IUPHAR/BPS	3951
ChemSpider	5293690
UNII	HW6NV07QEC
ChEMBL	CHEMBL1111
Chemical data
Formula	C22H22N2O4
Molecular mass	378.421 g/mol
	SMILES O=C(O)[C@@H](Oc1nc(cc(n1)C)C)C(OC)(c2ccccc2)c3ccccc3 ;
	InChI 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 ; Key:OUJTZYPIHDYQMC-LJQANCHMSA-N ;
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　　[★]

英: ambrisentan
商: ヴォリブリス
関: その他の循環器官用薬

[1] Vatter H, Seifert V (2006). "Ambrisentan, a non-peptide endothelin receptor antagonist". Cardiovasc Drug Rev 24 (1): 63–76. doi:10.1111/j.1527-3466.2006.00063.x. PMID 16939634.

[test-2] Frampton JE (2011). "Ambrisentan". American Journal of Cardiovascular Drugs 11 (4): 215–26. doi:10.2165/11207340-000000000-00000. PMID 21623643.

[3] Pollack, Andrew (2007-06-16). "Gilead’s Drug Is Approved to Treat a Rare Disease". New York Times. Archived from the original on 20 June 2007. Retrieved 2007-05-25.

[4] "U.S. Food and Drug Administration Approves Gilead's Letairis Treatment of Pulmonary Arterial Hypertension" (Press release). Gilead Sciences. 2007-06-15. Retrieved 2007-06-16.

[5] "FDA Approves New Orphan Drug for Treatment of Pulmonary Arterial Hypertension" (Press release). Food and Drug Administration. 2007-06-15. Archived from the original on 23 June 2007. Retrieved 2007-06-22.

[6] "GlaxoSmithKline's Volibris (ambrisentan) receives authorisation from the European Commission for the treatment of Functional Class II and III Pulmonary Arterial Hypertension" (Press release). GlaxoSmithKline. 2008-04-25. Archived from the original on 30 April 2008. Retrieved 2008-04-29.

[7] Waknine, Yael (2005-05-09). "International Approvals: Ambrisentan, Oral-lyn, Risperdal". Medscape. Retrieved 2007-06-16.

[8] 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.

[9] Galiè, Nazzareno; Barberà, Joan A.; Frost, Adaani E.; Ghofrani, Hossein-Ardeschir; Hoeper, Marius M.; McLaughlin, Vallerie V.; Peacock, Andrew J.; Simonneau, Gérald; Vachiery, Jean-Luc; Grünig, Ekkehard; Oudiz, Ronald J.; Vonk-Noordegraaf, Anton; White, R. James; Blair, Christiana; Gillies, Hunter; Miller, Karen L.; Harris, Julia H.N.; Langley, Jonathan; Rubin, Lewis J. (2015). "Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension". New England Journal of Medicine 373 (9): 834–44. doi:10.1056/NEJMoa1413687.

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ambrisentan