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| Clinical data | |
|---|---|
| Trade names | Tracleer, Stayveer, Safebo |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a605001 |
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| Routes of administration | By mouth |
| ATC code | |
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| Pharmacokinetic data | |
| Bioavailability | 50% |
| Protein binding | >98% |
| Metabolism | Liver |
| Eliminationhalf-life | 5 hours |
| Identifiers | |
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| CAS Number | |
| PubChemCID | |
| IUPHAR/BPS | |
| DrugBank |
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| ChemSpider |
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| UNII | |
| KEGG | |
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| ChEMBL | |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.171.206 |
| Chemical and physical data | |
| Formula | C27H29N5O6S |
| Molar mass | 551.62 g·mol−1 |
| 3D model (JSmol) | |
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Bosentan, sold under the brand nameTracleer among others, is a dualendothelin receptor antagonist medication used in the treatment ofpulmonary artery hypertension (PAH).[4][5]
Bosentan is available as film-coated tablets (62.5 mg or 125 mg) or as dispersable tablets for oral suspension (32 mg).[4]
Bosentan is used to treat people with moderatepulmonary arterial hypertension and to reduce the number of digital ulcers — open wounds on especially on fingertips and less commonly the knuckles — in people withsystemic scleroderma.[4][3][6]
Bosentan is contraindicated in people takingglyburide due to an increased risk of increased liver enzymes and liver damage when these two agents are taken together.[4]
Use of bosentan with cyclosporine is contraindicated because cyclosporine A has been shown to markedly increase serum concentration of bosentan.[4]
Bosentan causes harm to fetuses (teratogenic) and it may renderhormonal contraceptives ineffective.[4][3]
In the US it is only available from doctors who follow an FDA-mandatedrisk evaluation and mitigation strategy (REMS) with respect to risks to fetuses and its risks of causing liver damage.[7]
In addition to the risk of causing birth defects and of causing liver damage, bosentan has a high risk of causingedema,pulmonary veno-occlusive disease, decreasing sperm counts, and decreases inhemoglobin andhematocrit.[4][3]
Very common adverse effects (occurring in more than 10% of people) include headache,elevated transaminases, and edema. Common adverse effects (between 1% and 10% of people) include anemia, reduced hemoglobin, hypersensitivity reactions, skin inflammation, itchiness, rashes, red skin, flushing, fainting, heart palpitations, low blood pressure, nasal congestion,gastro-esophageal reflux disease, and diarrhea.[4][3]
Bosentan may renderhormonal contraceptives ineffective.[4][3]
Bosentan is a competitive antagonist ofendothelin-1 at the endothelin-A (ET-A) and endothelin-B (ET-B) receptors. Under normal conditions, endothelin-1 binding of ET-A receptors causesconstriction of the pulmonary blood vessels.[8] Conversely, binding of endothelin-1 to ET-B receptors has been associated with both vasodilation and vasoconstriction of vascular smooth muscle, depending on the ET-B subtype (ET-B1 or ET-B2) and tissue.[9] Bosentan blocks both ET-A and ET-B receptors, but is thought to exert a greater effect on ET-A receptors, causing a total decrease in pulmonary vascular resistance.[4]
After oral administration, maximum plasma concentrations of bosentan are attained within 3–5 hours and the terminal elimination half-life (t1/2) is about 5 hours in healthy adult subjects. The exposure to bosentan after intervenous and oral administration is about 2-fold greater in adult patients with pulmonary arterial hypertension than in healthy adult subjects.[10]
Absolute bioavailability of bosentan is about 50% in healthy subjects.[11] Peak plasma concentration of bosentan with the dispersable tablets for oral suspension is 14% less on average compared to peak concentration of the oral tablets.[4]
Bosentan is a substrate ofCYP3A4 andCYP2C9.CYP2C19 may also play a role in its metabolism.[4] It is also a substrate of the hepatic uptake transporter organic anion-transporting polypeptides (OATPs) OATP1B1, OATP1B3, and OATP2B1.[12][13]
Elimination of bosentan is mostly hepatic, with minimal contribution from renal and fecal excretion.[14]
Use of bosentan with cyclosporine is contraindicated because cyclosporine A has been shown to markedly increase serum concentration of bosentan.[4]
Bosentan was studied inheart failure in a trial called REACH-1 that was terminated early in 1997, due to toxicity at the dose that was being studied.[15]
It was approved for pulmonary artery hypertension in the US in November 2001,[4][16] and in the European Union in May 2002.[3][5]
By 2013, worldwide sales of bosentan were $1.57 billion. The patents on bosentan started expiring in 2015.[17]
