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The role of endothelin-1 (ET-1) and its receptor ET<jats:sub>A<\/jats:sub> in the pathogenesis of aSAH-induced vasospasm suggests antagonism of this receptor as promising asset for pharmacological treatment. Clazosentan is a potent ET<jats:sub>A<\/jats:sub> receptor antagonist for intravenous use currently under development for the prevention of aSAH-induced cerebral vasospasm. The pharmacokinetics of clazosentan are characterized by an intermediate clearance, a volume of distribution similar to that of the extracellular fluid volume, dose-proportional exposure, an elimination independent of drug-metabolizing enzymes, and a disposition mainly dependent on the hepatic uptake transporter organic anion transport polypeptide 1B1\/1B3. In healthy subjects, clazosentan leads to an increase in ET-1 concentration and prevents the cardiac and renal effects mediated by infusion of ET-1. In patients, it significantly reduced the incidence of moderate or severe vasospasm as well as post-aSAH vasospasm-related morbidity and mortality. Clazosentan is well tolerated up to the expected therapeutic dose of 15\u00a0mg\/h and, in aSAH patients, lung complications, hypotension, and anemia were adverse events more commonly reported following clazosentan than placebo. In summary, clazosentan has a pharmacokinetic, pharmacodynamic, and safety profile suitable to become a valuable asset in the armamentarium of therapeutic modalities to prevent aSAH-induced cerebral vasospasm.<\/jats:p>","DOI":"10.3389\/fphar.2020.628956","type":"journal-article","created":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T07:51:22Z","timestamp":1612425082000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Clinical Pharmacology of Clazosentan, a Selective Endothelin A Receptor Antagonist for the Prevention and Treatment of aSAH-Related Cerebral Vasospasm"],"prefix":"10.3389","volume":"11","author":[{"given":"Pierre-Eric","family":"Juif","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper","family":"Dingemanse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Ufer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1056\/NEJM198303173081103","article-title":"Cerebral arterial spasm\u2013a controlled trial of nimodipine in patients with subarachnoid hemorrhage","volume":"308","author":"Allen","year":"1983","journal-title":"N. 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