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Sitaxentan: Wikis

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Systematic (IUPAC) name
N-(4-chloro-3-methyl-1,2-oxazol-5-yl)-2-[2-(6-methyl-2 H-1,3-benzodioxol-5-yl)acetyl]thiophene-3-sulfonamide
CAS number 210421-64-0
ATC code C02KX03
PubChem 216235
Chemical data
Formula C 18H15ClN2O6S2  
Mol. mass 454.906 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability 70 to 100%
Protein binding >99%
Metabolism Hepatic (CYP2C9- and CYP3A4-mediated)
Half life 10 hours
Excretion Renal (50 to 60%)
Fecal (40 to 50%)
Therapeutic considerations
Licence data

EU EMEA:link

Pregnancy cat.  ?
Legal status Prescription Only (S4) (AU) POM (UK)
Routes Oral

Sitaxentan sodium (sometimes incorrectly spelled Sitaxsentan sodium) is marketed as Thelin, originally by Encysive Pharmaceuticals until Pfizer purchased Encysive in February 2008.

Sitaxentan (original research code, TBC-11251) is a small molecule that blocks the action of endothelin (ET) on the endothelin-A (ETA) receptor selectively (by a factor of 6000 compared to the ETB). It is a sulfonamide class endothelin receptor antagonist (ERA) and is undergoing Food and Drug Administration (FDA) review for treating pulmonary hypertension. The rationale for benefit compared to bosentan, a nonselective ET blocker, is negligible inhibition of the beneficial effects of ETB stimulation, such as nitric oxide production and clearance of ET from circulation. However, in clinical trials, the efficacy of sitaxentan has been much the same as bosentan, but the liver toxicity has been better. Dosing is once daily, as opposed to twice daily for bosentan. Therefore the general marketing strategy adopted for sitaxentan is to promote it as a more convenient and potentially safer drug than bosentan, though not necessarily more effective.


Regulatory status

Thelin has been approved for marketing in both the European Union (on 10 August 2006), in Canada[1] and in Australia (on 7 March 2007). By February 2008 it had been launched commercially in Germany, Austria, The Netherlands, the United Kingdom, Ireland, France, Spain and Italy.

On the Prescription Drug User Fee Act (PDUFA) target action date of 24 March 2006 the United States' FDA recommended an approvable status to Thelin but said it would not yet approve the product. On 24 July 2006 Thelin received a second approvable letter stating that efficacy outcome issues raised in the context of the STRIDE-2 study were still unresolved. In July 2007, Encysive commenced a formal dispute resolution process in a preliminary meeting with the FDA. However, in September 2007 the company announced that it was making preparations for another phase III clinical trial (intended to be named STRIDE-5) to overcome the FDA's deficiency claims concerning the New Drug Application, and that it would not pursue the dispute resolution process [2]. However, the takeover by Pfizer resulted in a reconfiguration and extension of these plans, which now include combination therapy with sildenafil. The Sitaxentan Efficacy and Safety Trial With a Randomized Prospective Assessment of Adding Sildenafil (SR-PAAS) is an ongoing program of three clinical trials conducted in the United States ( identifiers: NCT00795639, NCT00796666 and NCT00796510) with anticipated completion dates between June 2010 and January 2014.

Adverse effects

Adverse effects observed with Thelin are class effects of endothelin receptor antagonists, and include :

Because Thelin inhibits metabolism of warfarin, a decreased dose of warfarin is needed when co-administered with thelin. This is because warfarin acts to prevent blood from clotting, and if it remains unmetabolized, it can continue to thin the blood.

External links


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