Bosentan

4-tert- butyl-N- [6 - ( 2-hydroxyethoxy ) - 5 - (2- methoxyphenoxy) -2 - ( pyrimidin-2- yl) pyrimidin-4- yl ] benzenesulfonamide

• C27H29N5O6S (bosentan )
• C27H28N5NaO6S (bosentan · sodium salt)

C02KX01 Mechanism

Endothelin receptor antagonist

Endothelin is displaced from its ETA and ETB receptors, this results in a vasodilation and (pulmonary ) reduction in blood pressure

195-198 ° C

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Bosentan is an endothelin receptor antagonist and as ambrisentan, Thelin and sildenafil as so-called orphan drug for the treatment of rare pulmonary hypertension ( pulmonary hypertension ), WHO functional class III approved.

Pharmacology

Mechanism of action and other applications

Bosentan displaced as an antagonist, the Endothelin-1, the most potent known endogenous Blutgefäßkonstringenz of its receptors ( ET1A and ET1B receptors), and thus removes the endothelin -1 action, so that the vessels dilate, so the increase caused by endothelin of ( pulmonary ) blood pressure is counteracted and there is a ( pulmonary ) blood pressure reduction. In addition, as caused by endothelin change of the blood vessels, the ( remodeling ) is reduced.

The substance is recently also in scleroderma, since extensive studies have positive results for the prevention of vacancies, eg at the fingertips, provided.

Side effects

Flush pathologies, edema and hypotension are previously documented as a result of the intervention in the regulation of blood pressure as side effects. Nonspecific side effects such as headaches, fatigue and itching can just as disorders of the gastrointestinal tract ( dyspepsia and reflux disease ) can occur. More often, it may result in hepatic transaminase elevations, so regular blood tests are necessary.

Interactions and contraindications

Contraindications are:

• Pregnancy - due to a reproductive toxicity
• Liver cirrhosis with a Child- Pugh score of class B and C
• Other liver dysfunction with elevated liver transaminase values

Due to the interaction with cyclosporin A via a CYP3A4 mechanism, concomitant administration of bosentan and cyclosporine A is also considered a contraindication because it may occur three to four times the plasma concentrations of bosentan and a halving of the plasma concentration of ciclosporin A.

Different strengths and dosage

The drug is available in dosage strengths 32 mg, 62.5 mg and 125 mg.

In an adult, the therapy is initiated in both the pulmonary hypertension as well as scleroderma 62.5 mg twice a day over a period of four weeks and then increased to the standard maintenance dose of 125 mg twice daily.

Trade names

In Germany and Austria the Bosentanpräparat, manufactured by Actelion is marketed under the trade name Tracleer ®.