title: Sitaxsentan for treatment of pulmonary hypertension.
abstract: OBJECTIVE
  To review the literature pertinent to the efficacy and safety of sitaxsentan, a selective endothelin (ET)-A receptor antagonist under evaluation for the treatment of pulmonary arterial hypertension (PAH).
  
  
  METHODS
  Articles were identified through searches of the MEDLINE (1966-November 2006) and International Pharmaceutical Abstracts (1970-November 2006) databases, using the key words endothelin antagonist, pulmonary arterial hypertension, pulmonary hypertension, sitaxsentan, and TBC11251. Searches were limited to articles published in English.
  
  
  METHODS
  Due to the limited number of articles on sitaxsentan, all studies captured in the search results were evaluated.
  
  
  RESULTS
  Four studies of sitaxsentan in humans with PAH have been published to date. An uncontrolled open-label study and a randomized placebo-controlled study (STRIDE-1; Sitaxsentan to Relieve Impaired Exercise-1) showed sitaxsentan to improve exercise tolerance in patients with PAH, as evidenced by significant increases in the distance walked in 6 minutes. Significant hepatotoxicity developed in patients receiving sitaxsentan 300 mg. The benefits of sitaxsentan with respect to exercise tolerance and hemodynamics were sustained in a one year extension of the placebo-controlled study. The results of a multicenter, randomized, placebo-controlled trial of 2 doses of sitaxsentan with an open-label bosentan arm (STRIDE-2) suggested that only the 100 mg dose provided superior benefit in exercise tolerance and improvement in functional class. Treatment-related adverse effects were similar for all groups.
  
  
  CONCLUSIONS
  Sitaxsentan appears to be superior to placebo in improving exercise tolerance in patients with PAH but may produce therapeutic outcomes similar to those of bosentan, a comparator agent. The optimal dose of sitaxsentan appears to be 100 mg once daily. Information about the use of sitaxsentan in a greater number of patients with PAH for longer periods is necessary to further define its place in the treatment of PAH.
authors.affiliation: Department of Pharmacy Practice and Pharmacy Administration, Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, Philadelphia, PA 19104, USA. e.wittbr@usip.edu
authors.forename: Eric T
authors.initials: ET
authors.lastname: Wittbrodt
authors.forename: Amina
authors.initials: A
authors.lastname: Abubakar
mesh_terms: D000818:Animals; D065128:Endothelin Receptor Antagonists; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology / Q000627:therapeutic use*; D017466:Receptors, Endothelin / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D065128:Endothelin Receptor Antagonists; D007555:Isoxazoles; D017466:Receptors, Endothelin; D013876:Thiophenes; C106276:sitaxsentan