Bosentan is an endothelin receptor antagonist (ERA) manufactured by Actelion Pharmaceuticals in the United States, the European Union and other countries under the trade name Tracleer that is used to treat patients with pulmonary arterial hypertension (PAH).
Denoted chemically as 4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)[2,2´]-bipyrimidin-4-yl]- benzenesulfonamide monohydrate, bosentan is aimed at improving the ability to exercise in patients with symptoms in WHO Group 1 and reduce disease progression by slowing clinical deterioration. Endothelin is responsible for vasoconstriction and elevation of blood pressure, and bosentan helps dilate blood vessels to normalize blood flow through the pulmonary artery.
How Tracleer (Bosentan) Works
Brosentan is a competitive antagonist of the protein endothelin-1 (ET-1). ET-1 is a protein molecule responsible for both autocrine (same cell) and paracrine (cell to cell) signaling, and ETA and ETB are receptors responsible for binding of ET-1 to mediate their effects on vascular smooth muscle. ETA is responsible for vasoconstriction and cell proliferation and ETB mediates vasodilation, anti-proliferation, and ET-1 clearance. In patients with PAH, there is a tenfold increase in the amount of plasma ET-1 concentration, along with a ninefold increase in pulmonary arterial endothelium and an increase in vasoconstriction indicates a rise in ETA levels as well. In these cases, brosentan acts as the antagonist for these ET-1 peptides, with a strong affinity for ETA receptors. Blocking this interaction reduces pulmonary vascular resistance and ensures vasodilation.
Clinical Trials for Tracleer (Bosentan)
Tracleer was approved by the U.S. FDA for use in patients with WHO functional classes II to IV PAH in August 2009. This approval came in the wake of results from a Phase 3 clinical trial titled Endothelin Antagonist Trial in Mildly Symptomatic PAH Patients (EARLY) showed considerable reduction in pulmonary vascular resistance (22.6 percent) and a 77 percent decrease in clinical worsening of the disease. The 24-week trial of Tracleer was tested against a placebo, and the results were measured via a 6 minute walk distance (6MWD) test.
Dosing for Tracleer (Bosentan)
Tracleer is an oral formulation, with tablets available in both 62.5 mg and 125 mg. It is taken with or without food, twice daily unless prescribed otherwise. Common side effects of the drug include swelling of the limbs, headache, nausea, dizziness, stomach upset, and flushing. Serious side effects include jaundice, dark-colored urine and stool, severe allergic reactions and breathing difficulties.
Patients with liver or renal comorbidities should consult a specialist before taking the drug. Patients already taking drugs like bosutinib, cabazitaxel, cyclosporine, or glyburide should refrain from using the drug, as should women who are pregnant or are planning to do so. Hepatotoxicity and anemia are also potential side effects of the drug, so regular liver-function tests and hematocrit monitoring are necessary during the course of the treatment.
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