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• DRUGBANK - Bosentan
• indication:

  Used in the treatment of pulmonary arterial hypertension (PAH), to improve exercise ability and to decrease the rate of clinical worsening (in patients with WHO Class III or IV symptoms).

• pharmacology:

• mechanism:

  Endothelin-1 (ET-1) is a neurohormone, the effects of which are mediated by binding to ET<sub>A</sub> and ET<sub>B</sub> receptors in the endothelium and vascular smooth muscle. ET-1 concentrations are elevated in plasma and lung tissue of patients with pulmonary arterial hypertension, suggesting a pathogenic role for ET-1 in this disease. Bosentan is a specific and competitive antagonist at endothelin receptor types ET<sub>A</sub> and ET<sub>B</sub>. Bosentan has a slightly higher affinity for ET<sub>A</sub> receptors than for ET<sub>B</sub> receptors.

• toxicity:

  Bosentan has been given as a single dose of up to 2400 mg in normal volunteers, or up to 2000 mg/day for 2 months in patients, without any major clinical consequences. The most common side effect was headache of mild to moderate intensity. In the cyclosporine A interaction study, in which doses of 500 and 1000 mg b.i.d. of bosentan were given concomitantly with cyclosporine A, trough plasma concentrations of bosentan increased 30-fold, resulting in severe headache, nausea, and vomiting, but no serious adverse events. Mild decreases in blood pressure and increases in heart rate were observed. There is no specific experience of overdosage with bosentan beyond the doses described above. Massive overdosage may result in pronounced hypotension requiring active cardiovascular support.

• absorprion:

  Absolute bioavailability is approximately 50% and food does not affect absorption.

• halflife:

  Terminal elimination half-life is about 5 hours in healthy adult subjects.

• roouteelimination:

  Bosentan is eliminated by biliary excretion following metabolism in the liver.

• volumedistribution:

  * 18 L

• clearance:

  * 4 L/h [patients with pulmonary arterial hypertension]