QuickView for Bosentan (compound)

Summary
General Info

PubChem

PubChem Compound 104865

Name:	bosentan
PubChem Compound ID:	104865
Molecular formula:	C₂₇H₂₉N₅O₆S
Molecular weight:	551.615 g/mol
Synonyms:	Ro-47-0203/039; Tracleer; Bosentan; Ro-47-0203/029; Benzenesulfonamide, 4-(1,1-dimethylethyl)-N-(6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)(2,2'-bipyrimidin)-4-yl)-; Ro-47-0203; 147536-97-8; p-tert-Butyl-N-(6-(2-hydroxyethoxy)-5-(o-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl)benzenesulfonamide; Ro 47-0203; 174227-18-0. show more » Ro-47-0203/039; Tracleer; Bosentan; Ro-47-0203/029; Benzenesulfonamide, 4-(1,1-dimethylethyl)-N-(6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)(2,2'-bipyrimidin)-4-yl)-; Ro-47-0203; 147536-97-8; p-tert-Butyl-N-(6-(2-hydroxyethoxy)-5-(o-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl)benzenesulfonamide; Ro 47-0203; 174227-18-0; Ro 47-0203/039; 4-(1,1-Dimethylethyl)-N-(6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-(2,2'-bipyrimidin)-4-yl)benzenesulfornamide show less «

DrugBank

Identification

Name:	bosentan
Name (isomeric):	DB00559
Drug Type:	small molecule
Synonyms:	Bosentan hydrate
Brand:	Tracleer
Category:	Antihypertensive Agents
CAS number:	147536-97-8

Pharmacology

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:	Bosentan belongs to a class of drugs known as endothelin receptor antagonists (ERAs). Patients with PAH have elevated levels of endothelin, a potent blood vessel constrictor, in their plasma and lung tissue. Bosentan blocks the binding of endothelin to its receptors, thereby negating endothelin's deleterious effects.
Mechanism of Action:	Endothelin-1 (ET-1) is a neurohormone, the effects of which are mediated by binding to ET_A and ET_B 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... show more » Endothelin-1 (ET-1) is a neurohormone, the effects of which are mediated by binding to ET_A and ET_B 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_A and ET_B. Bosentan has a slightly higher affinity for ET_A receptors than for ET_B receptors. show less «
Absorption:	Absolute bioavailability is approximately 50% and food does not affect absorption.
Protein binding:	Greater than 98% to plasma proteins, mainly albumin.
Biotransformation:	Bosentan is metabolized in the liver by the cytochrome P450 enzymes CYP2C9 and CYP3A4 (and possibly CYP2C19), producing three metabolites, one of which, Ro 48-5033, is pharmacologically active and may contribute 10 to 20% to the total activity of the parent compound.
Route of elimination:	Bosentan is eliminated by biliary excretion following metabolism in the liver.
Half Life:	Terminal elimination half-life is about 5 hours in healthy adult subjects.
Clearance:	4 L/h [patients with pulmonary arterial hypertension]
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.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Take without regard to meals.

Drug interaction:

Tramadol	Bosentan may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Dicumarol	Bosentan may decrease the anticoagulant effect of dicumarol by increasing its metabolism.
Mestranol	Decreases the effect of contraceptive
Norethindrone	Bosentan may decrease the contraceptive effect of norethindrone. Hormonal contraception should not be relied on alone during concomitant therapy with bosentan.
Cyclosporine	Cyclosporine may increase the effect and toxicity of bosentan.

Tramadol	Bosentan may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Dicumarol	Bosentan may decrease the anticoagulant effect of dicumarol by increasing its metabolism.
Mestranol	Decreases the effect of contraceptive
Norethindrone	Bosentan may decrease the contraceptive effect of norethindrone. Hormonal contraception should not be relied on alone during concomitant therapy with bosentan.
Cyclosporine	Cyclosporine may increase the effect and toxicity of bosentan.
Medroxyprogesterone	Bosentan may decrease the contraceptive effect of medroxyprogesterone. Hormonal contraception should not be relied on alone during concomitant therapy with bosentan.
Ketoconazole	Ketoconazole may increase the effect and toxicity of bosentan.
Acenocoumarol	Bosentan may decrease the anticoagulant effect of acenocoumarol by increasing its metabolism.
Ethinyl Estradiol	Bosentan may decrease the contraceptive effect of ethinyl estradiol. Hormonal contraception should not be relied on alone during concomitant therapy with bosentan.
Anisindione	Bosentan may decrease the anticoagulant effect of anisindione by increasing its metabolism.
Itraconazole	Itraconazole may increase the effect and toxicity of bosentan.
Trazodone	The CYP3A4 inducer, Bosentan, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Bosentan is initiated, discontinued or dose changed.
Cerivastatin	Bosentan may decrease the serum concentration of cerivastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of cerivastatin if bosentan is initiated, discontinued or dose changed.
Temsirolimus	Bosentan may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Atorvastatin	Bosentan may decrease the serum concentration of atorvastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if bosentan is initiated, discontinued or dose changed.
Warfarin	Bosentan may decrease the anticoagulant effect of warfarin by increasing its metabolism.
Glyburide	Increased risk of hepatic toxicity
Lovastatin	Bosentan may decrease the serum concentration of lovastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if bosentan is initiated, discontinued or dose changed.
Telithromycin	Co-administration may cause decreased Telithromycin and increased Bosentan plasma concentrations. Consider alternate therapy.
Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of bosentan by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of bosentan if voriconazole is initiated, discontinued or dose changed.
Tolbutamide	Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Bosentan. Consider alternate therapy or monitor for changes in Bosentan therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Simvastatin	Bosentan may decrease the serum concentration of simvastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of simvastatin if bosentan is initiated, discontinued or dose changed.

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Targets

Endothelin-1 receptor

Endothelin B receptor

Enzymes

Cytochrome P450 3A4

Cytochrome P450 2C9

Transporters

Bile salt export pump