Bosentan

Bosentan

Bosentan
Systematic (IUPAC) name
4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]benzene-1-sulfonamide
Clinical data
Trade names Tracleer
AHFS/Drugs.com
MedlinePlus
Pregnancy
category
  • X
Legal status
  • (Prescription only)
Routes of
administration
Oral
Pharmacokinetic data
Bioavailability 50%
Protein binding >98%
Metabolism Hepatic
Biological half-life 5 hours
Identifiers
CAS Registry Number  Y
ATC code C02
PubChem CID:
IUPHAR/BPS
DrugBank  Y
ChemSpider  Y
UNII  Y
KEGG  N
ChEBI  Y
ChEMBL  Y
Chemical data
Formula C27H29N5O6S
Molecular mass 551.614 g/mol
 N   

Bosentan is a dual endothelin receptor antagonist used in the treatment of pulmonary artery hypertension (PAH). It is licensed in the United States, the European Union and other countries by Actelion Pharmaceuticals for the management of PAH under the trade name Tracleer.

Contents

  • Mechanism of action 1
  • Clinical uses 2
  • Warnings 3
  • See also 4
  • References 5
  • External links 6

Mechanism of action

Bosentan is a competitive antagonist of endothelin-1 at the endothelin-A (ET-A) and endothelin-B (ET-B) receptors. Under normal conditions, endothelin-1 binding of ET-A or ET-B receptors causes constriction of the pulmonary blood vessels. By blocking this interaction, bosentan decreases pulmonary vascular resistance. Bosentan has a slightly higher affinity for ET-A than ET-B.[1]

Clinical uses

Bosentan is indicated mainly for the treatment of pulmonary hypertension. In 2007, Bosentan was also approved in the European Union for reducing the number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcer disease.

In the United States, Bosentan is indicated for the treatment of pulmonary arterial hypertension (WHO Group I) in patients with WHO Class II-IV symptoms, to improve exercise capacity and decrease the rate of clinical worsening.[2]

Warnings

Due to potential hepatotoxicity, the FDA requires monthly monitoring of liver function tests while taking Bosentan.

Bosentan use requires hematocrit monitoring due to potential onset of anemia.[3]

Hormone-based contraception is not possible in women taking Bosentan, due to a pharmacokinetic interaction.[4] Therefore, other highly reliable forms of contraception should be used instead.

Bosentan is contraindicated in pregnancy because of its teratogenicity (Pregnancy Category X). [5] [6]

See also

References

  1. ^ Funke C, Farr M, Werner B, Dittmann S, Uberla K, Piper C, Niehaus K, Horstkotte D (Apr 2010). "Antiviral effect of Bosentan and Valsartan during coxsackievirus B3 infection of human endothelial cells.". Journal of General Virology 91 (8): 1959–1570.  
  2. ^ http://www.tracleer.com/pdf/09%20276%2001%2000%200809_Tra%20PI_4%20Pg_081409pdf.pdf
  3. ^ http://www.ionchannels.org/showabstract.php?pmid=15875338
  4. ^ http://www.ionchannels.org/showabstract.php?pmid=15875338
  5. ^ http://www.medicinescomplete.com/mc/bnf/current/PHP1044-bosentan.htm?q=bosentan&t=search&ss=text&p=1#_hit
  6. ^ http://www.nzf.org.nz/nzf_1183.html

External links

  • PubPK - Bosentan pharmacokinetics
  • Tracleer official website
  • - Tracleer Prescribing Information