Home | News | Kontakt | Sitemap | Impressum

Medical > Therapy > Specific treatments

Endothelin receptor antagonists
Bosentan

 

Bosentan is a dual endothelin receptor antagonist (ERA) with affinity for both endothelin ETA and ETB receptors (Ray et al. 2000). After the encouraging results of double-blind, placebo-controlled pilot trial (Channick et al. 2001) comparing placebo in 32 patients with PAH oral bosentan 62.5 mg bid. for four weeks and then 125 mg bid. for a minimum of 12 weeks showing difference in the 6-minute walking distance of 76 m compared to placebo as well as an improvement in hemodynamics, dyspnea score and functional class, a lager double-blind placebo-controlled trial (BREATHE-1) was conducted comparing 96 patients receiving placebo, 74 receiving 2 x 62.5 mg and then from week four a dose of 2 x 125 mg and 70 patients receiving a dose from week four of 2 x 250 mg (Rubin et al. 2002). After 16 weeks there was a mean difference of 44 m in the distance walked in 6 minutes in favor of the combined bosentan groups as well as an improvement in the dyspnea score and the WHO functional class. During an extended course of treatment of 28 weeks bosentan significantly lengthened the time to clinical worsening compared with the placebo group. Bosentan was generally well tolerated, the only significant adverse side effect were elevations in aminotransferase levels of more than three times the upper level, which occurred in overall 14 % of the patients receiving bosentan. Elevations of more than eight times of the upper level occurred in 7 % of the patients receiving 250 mg bosentan twice daily compared to 3 % of those receiving 125 mg bosentan twice daily. Because of this and the fact that functionally patients receiving the higher bosentan dose had only a slight, non-significant greater improvement in 6-minute walking distance, bosentan dose of a 125 mg twice daily is now recommended for long-term treatment. Regular monitoring of hepatic function is crucial in the surveillance of these patients.

References

Back to > Medical > Therapy > Specific treatments