Ambrisentan
Synonym(s):(+)-(2S)-2-[(4,6-dimethylpyrimidin-2-yl)oxy]-3-methoxy-3,3-diphenylpropanoic acid
- CAS NO.:177036-94-1
- Empirical Formula: C22H22N2O4
- Molecular Weight: 378.42
- MDL number: MFCD09842330
- EINECS: 658-059-9
- SAFETY DATA SHEET (SDS)
- Update Date: 2024-05-08 15:48:27
What is Ambrisentan?
Absorption
Ambrisentan is rapidly absorbed with peak plasma concentrations occuring around 2 hours after oral administration. Cmax and AUC increase proportionally with dose across the therapeutic dosing range. Absolute oral bioavailability of ambrisentan is unknown. Absorption is not affected by food.
Toxicity
Ambrisentan is teratogenic and has a high risk of embryo-fetal toxicity. LD50 was found to be greater than or equal to 3160 mg/kg when studied in rats. There was no evidence of carcinogenic potential in 2 year oral daily dosing studies in rats and mice.
Description
Ambrisentan is a selective endothelin-A (ETA) receptor antagonist introduced for the oral treatment of patients with pulmonary arterial hypertension (PAH), to improve exercise capacity and delay clinical worsening. It is the third ET-receptor antagonist to be marketed for this indication behind bosentan and sitaxsentan. PAH is a rare disease of the small pulmonary arteries characterized by vascular proliferation and remodeling, resulting in a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, and ultimately, right ventricular failure and premature death. Early symptoms of PAH include gradual onset of shortness of breath, fatigue, palpitation, edema, and fainting. Endothelin-1 (ET-1), a potent vasoconstrictor and smooth muscle mitogen, is a key contributor to the acceleration of the disease, and its effects are mediated through activation ofETA and ETB receptors.
The Uses of Ambrisentan
Nonpeptide endothelin ETA receptor antagonist. Antihypertensive
What are the applications of Application
Ambrisentan is a nonpeptide endothelin ETAR (ETA receptor) antagonist and antihypertensive
Background
Ambrisentan is an orally active selective type A endothelin receptor antagonist indicated for the treatment of pulmonary arterial hypertension. It is approved in Europe, Canada and the United States for use as a single agent to improve exercise ability and delay clinical worsening. In addition, it is approved in the United States for use in combination with tadalafil to reduce the risks of disease progression, hospitalization and to improve exercise ability. Studies establishing the efficacy of Ambrisentan included patients with both idiopathic or heritable pulmonary arterial hypertension and those with pulmonary arterial hypertension associated with connective tissue diseases. Patients studied displayed symptoms and etiologies predominantly of WHO Functional Class II-III. As an endothelin receptor antagonist, Ambrisentan prevents endogenous endothelin peptide from constricting the muscles in blood vessels, allowing them to relax and permit a reduction in blood pressure.
Indications
Ambrisentan is indicated for treatment of idiopathic (‘primary’) pulmonary arterial hypertension (IPAH) and pulmonary arterial hypertension (PAH) associated with connective tissue disease in patients with WHO functional class II or III symptoms. In the United States of America, ambrisentan is also indicated in combination with tadalafil to reduce the risks of disease progression and hospitalization for worsening PAH, and to improve exercise ability.
Pharmacokinetics
Ambrisentan 10 mg daily had no significant effect on the QTc interval, whereas a 40 mg daily dose of ambrisentan increased mean QTc at tmax by 5 ms with an upper 95% confidence limit of 9 ms. Significant QTc prolongation is not expected in patients taking ambrisentan without concomitant metabolic inhibitors. Plasma concentrations of B-type natriuretic peptide (BNP) in patients who received ambrisentan for 12 weeks were significantly decreased. Two Phase III placebo-controlled studies demonstrated a decrease in BNP plasma concentrations by 29% in the 2.5 mg group, 30% in the 5 mg group, and 45% in the 10 mg group (p < 0.001 for each dose group) and an increase by 11% in the placebo group.
Metabolism
Ambrisentan is a metabolized primarily by uridine 5’-diphosphate glucuronosyltransferases (UGTs) 1A9S, 2B7S,1A3S to form ambrisentan glucuronide. Ambrisentan is also metabolized to a lesser extent by CYP3A4, CYP3A5 and CYP2C19 to form 4- hydroxymethyl ambrisentan which is further glucuronidated to 4-hydroxymethyl ambrisentan glucuronide.
Properties of Ambrisentan
Melting point: | >150°C (dec.) |
Boiling point: | 551.1±60.0 °C(Predicted) |
Density | 1.228±0.06 g/cm3(Predicted) |
storage temp. | Sealed in dry,2-8°C |
solubility | DMSO (Slightly), Methanol (Slightly) |
form | Solid |
color | White to Off-White |
Safety information for Ambrisentan
Signal word | Danger |
Pictogram(s) |
Health Hazard GHS08 |
Precautionary Statement Codes |
P201:Obtain special instructions before use. P308+P313:IF exposed or concerned: Get medical advice/attention. |
Computed Descriptors for Ambrisentan
Abamectin manufacturer
Ralington Pharma
KPS Chemicals And Pharmaceuticals
Enaltec Labs Pvt Ltd
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