Bosentan

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Structural formula
Structure of bosentan
General
Non-proprietary name Bosentan
other names

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

Molecular formula
  • C 27 H 29 N 5 O 6 S (bosentan)
  • C 27 H 28 N 5 NaO 6 S (bosentan sodium salt )
External identifiers / databases
CAS number
  • 147536-97-8 (bosentan)
  • 150726-52-6 (bosentan sodium salt)
EC number 643-099-1
ECHA InfoCard 100.171.206
PubChem 104865
ChemSpider 94651
DrugBank DB00559
Wikidata Q419769
Drug information
ATC code

C02 KX01

Drug class

Endothelin receptor antagonist

Mechanism of action

Endothelin is displaced by its ET A and ET B receptors, resulting in vascular dilatation and (pulmonary) blood pressure lowering

properties
Molar mass 551.62 g mol −1
Physical state

firmly

Melting point

195–198 ° C (sodium salt)

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
08 - Dangerous to health

Caution

H and P phrases H: 361-412
P: ?
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Bosentan is an endothelin receptor antagonist and is approved as a so-called orphan drug for the treatment of the rare pulmonary arterial hypertension (pulmonary high blood pressure) of the functional WHO class III.

pharmacology

Mechanism of action and other areas of application

Bosentan displaced as antagonist the endothelin -1, the most potent known endogenous Blutgefäßkonstringenz of its receptors (ET 1A - and ET 1B receptors) and therefore cancels the effect of endothelin-1, so that the vessels dilate, so the by endothelin The increase in ( pulmonary ) blood pressure caused is counteracted and a (pulmonary) blood pressure decrease occurs. In addition, the change in blood vessels caused by endothelin, known as remodeling , is reduced.

The substance has recently also been used in scleroderma , as extensive studies have shown positive results in preventing vacancies, e.g. B. on the fingertips have provided.

Side effects

Flush symptoms, edema and hypotension have so far been documented as side effects as a result of the intervention in blood pressure regulation. Nonspecific side effects such as headache, tiredness and itching can occur, as well as disorders of the gastrointestinal tract ( dyspepsia and reflux disease ). Increased liver transaminases may occur more frequently , so that regular blood tests are necessary.

Interactions and contraindications

The following are considered contraindications:

Due to the interaction with ciclosporin A via a CYP3A4 mechanism, the simultaneous administration of bosentan and ciclosporin A is also considered a contraindication, as this can lead to three to four times the plasma concentrations of bosentan and halve the plasma concentration of ciclosporin A.

Potency and dosage

The preparation is available in strengths of 32 mg, 62.5 mg and 125 mg.

In an adult, therapy for both pulmonary hypertension and scleroderma is started with 62.5 mg twice daily for four weeks and then increased to the standard maintenance dose of 125 mg twice daily.

Trade names

In Germany and Austria , the bosentan preparation manufactured by Actelion is marketed under the trade name Tracleer. Since 2017, the active ingredient has also been available generically from various companies in Germany, but the generics are currently not available through pharmacy wholesalers, but only through direct sales.

Individual evidence

  1. ^ The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, p. 221, ISBN 978-0-911910-00-1 .
  2. ↑ Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of (2S) -3-methyl-2- [pentanoyl - [[2 '- (1H-tetrazol-5-yl) phenyl] phenyl] -4-ylmethyl] amino] butanoic Template: link text check / apostrophe is shown, which is derived from a self-classification by the distributor acid in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on December 28, 2019.
  3. ↑ a b c d e ABDA database (as of July 17, 2008) of DIMDI .
  4. ↑ Pharmazeutische Zeitung No. 27 of July 3, 2008, p. 24 ff.
  5. ↑ European Medicines Agency: Tracleer .
  6. ↑ Austria Codex (as of July 17, 2008).
  7. ↑ Apotheke Adhoc: Tracleer Generics: Not through wholesalers . In: APOTHEKE ADHOC . ( apotheke-adhoc.de [accessed on September 27, 2017]).