Ambrisentan

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 Y
ATC code	C02KX02 (WHO)
PubChem	CID: 6918493
IUPHAR/BPS	3951
ChemSpider	5293690 Y
UNII	HW6NV07QEC Y
ChEMBL	CHEMBL1111 Y
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 Y Key:OUJTZYPIHDYQMC-LJQANCHMSA-N Y
(verify)

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

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.
8/27/2015 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.

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
• Information on the LETAIRIS Education and Access Program (LEAP)