Читать книгу Transporters and Drug-Metabolizing Enzymes in Drug Toxicity - Albert P. Li - Страница 74

Sitaxentan is a benzodioxole drug marketed for the treatment of pulmonary arterial hypertension (PAH) [150, 151]. It also has been found to be an effective treatment of digital ulcers, easing pain, and preventing the formation of new ulcers [152]. It is a competitive antagonist of endothelin‐1 which has been found to be elevated in PAH patients [153]. Binding of endothelin‐1 to its receptors, endothelin‐A (ET‐A) and endothelin‐B (ET‐B), leads to pulmonary vasoconstriction [153]. Inhibition of endothelin‐1 binding to its receptors by Sitaxentan thereby inhibits the vasoconstriction effects of endothelin, leading to decreases in pulmonary vascular resistance [150, 151]. Sitaxentan was found to be associated with idiosyncratic acute liver failures [154–157], resulting in deaths and a need for liver transplantation. Sitaxentan was withdrawn from the market worldwide in 2010.