Bosentan

Bosentan is a drug that belongs to the class of endothelin receptor antagonists. It received approval for treating pulmonary artery hypertension (PAH) in the United States in November 2001 and in the European Union in May 2002. The medication aids in enhancing exercise capacity and slows the advancement of symptoms in individuals with PAH. Bosentan works by inhibiting the action of endothelin, a substance that constricts blood vessels, thus allowing for better blood flow in those with pulmonary artery hypertension.

BRAND NAMES:

Stayveer – Stayveer comes in film-coated tablets containing bosentan monohydrate as the main active ingredient with strength 62.5mg and 125mg.

Tracleer – Tracleer is available in film-coated tablets with strength 62.5mg and 125mg containing bosentan monohydrate as the main active ingredient.

MECHANISM OF ACTION:

Endothelins are a group of peptides composed of two amino acids, with three isoforms: ET-1, ET-2, and ET-3. ET-1 is the most prevalent and is found in various locations, including the airway epithelium, lung parenchymal cells, pulmonary tumors, pulmonary vasculature, kidneys, small intestine, and cardiac myocytes. Once produced and secreted, endothelins bind to endothelin G protein-coupled receptors, which include two main types: endothelin A (ETA) and endothelin B (ETB). While these receptors are present throughout lung tissue, ETA receptors are most concentrated in the pulmonary vasculature and airway smooth muscle, whereas ETB receptors are primarily found in the endothelium.

PHARMACOKINETICS:

Absorption: Bosentan reaches peak plasma concentrations after approximately 3 hours. The absolute bioavailability is about 50%.

Distribution: The terminal half-life after oral administration is 5.4 hours and is unchanged at a steady state. The plasma protein binding is greater than 98% mainly albumin.

Metabolism: It is mainly metabolized through hepatic metabolism. Three metabolites have been identified, formed by cytochrome P450(CYP) 2C9 and 3A4.

Excretion: Bosentan is cleared from the body through biliary excretion after being metabolized in the liver.

DOSAGE AND ADMINISTRATION:

Bosentan is available in the form of tablets and oral suspensions. Depending on the patient's condition and age the dosage will be recommended.

For treating pulmonary artery hypertension, bosentan is given twice daily at 125mg or 250mg for adults.

For patients less than 12 years old, the recommended dose ranges from 31.25mg to 125mg twice daily.

DRUG INTERACTIONS:

Before taking bosentan it is required to discuss with the health care provider if the patient is taking treatment for other diseases. Some medications might cause serious adverse effects while taking along with bosentan. Below are the medications that should be avoided while taking bosentan or should be taken as per the doctor's reference.

Cyclosporine increases serum levels of bosentan.
Glyburide can increase the risk of serum transaminase elevations.
Bosentan decreases the serum concentrations of oral contraceptive pills.
CYP3A4 inhibitors like clarithromycin and erythromycin may increase serum concentrations or effects of bosentan.
Carbamazepine, phenytoin, rifampin, and isoenzyme CYP3A4 inducers decrease bosentan serum concentrations or effects.
St. John Wort, the herbal medicine decreases the serum concentrations of bosentan.

FOOD INTERACTIONS:

The absorption of medicine isn’t affected by food.

CONTRAINDICATIONS:

Hypersensitive to bosentan or any of its components, concurrent use of cyclosporine and glyburide.

ADVERSE EFFECTS: