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  • A review of pulmonary arterial hypertension: role of ambrisentan
  • Barst RJ
  • Vasc Health Risk Manag 2007[]; 3 (1): 11-22
  • Pulmonary arterial hypertension (PAH) is a rare fatal disease. Current disease-specific therapeutic interventions in PAH target 1 of 3 established pathways in disease pathobiology: prostacyclin, nitric oxide, and endothelin-1. Endothelin receptor antagonists (ERAs) act on the endothelin pathway by blocking binding of endothelin-1 to its receptors (endothelin type-A [ET(A)] and/or type-B [ET(B)]) on the surface of endothelial and smooth muscle cells. Ambrisentan is an oral, once-daily, ET(A)-selective ERA in development for the treatment of PAH. In Phase 3 clinical trials in patients with PAH, ambrisentan (2.5-10 mg orally once-daily) improved exercise capacity, Borg dyspnea index, time to clinical worsening, WHO functional class, and quality of life compared with placebo. Ambrisentan provided durable (at least 2 years) improvement in exercise capacity in a Phase 2 long-term extension study. Ambrisentan was well tolerated with a lower incidence and severity of liver function test abnormalities compared with the ET(A)/ET(B) ERA, bosentan, and the ET(A)-selective ERA, sitaxsentan. Ambrisentan does not induce or inhibit P450 enzymes; therefore, ambrisentan is unlikely to affect the pharmacokinetics of P450-metabolized drugs. The demonstration of clinical efficacy, low incidence of acute hepatic toxicity, and low risk of drug-drug interactions support the role of ambrisentan for the treatment of PAH.
  • |Endothelin Receptor Antagonists[MESH]
  • |Endothelin-1/blood/drug effects[MESH]
  • |Exercise/physiology[MESH]
  • |Humans[MESH]
  • |Hypertension, Pulmonary/blood/*drug therapy/physiopathology[MESH]
  • |Muscle, Smooth, Vascular/drug effects/physiopathology[MESH]
  • |Phenylpropionates/pharmacokinetics/*therapeutic use[MESH]
  • |Pulmonary Wedge Pressure/drug effects/physiology[MESH]
  • |Pyridazines/pharmacokinetics/*therapeutic use[MESH]
  • |Receptors, Endothelin/blood[MESH]
  • |Treatment Outcome[MESH]
  • |Vascular Resistance/drug effects[MESH]

  • *{{pmid17583171}}
    *<b>[ A review of pulmonary arterial hypertension: role of ambrisentan ]</b> Vasc Health Risk Manag 2007; 3(1) ; 11-22 Barst RJ


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    Vasc Health Risk Manag

    11 1.3 2007