448:
29:
657:. The Sitaxentan Efficacy and Safety Trial With a Randomized Prospective Assessment of Adding Sildenafil (SR-PAAS) was an ongoing program of three clinical trials conducted in the United States (ClinicalTtrials.gov identifiers: NCT00795639, NCT00796666 and NCT00796510) with anticipated completion dates between June 2010 and January 2014.
648:
In March 2006, the FDA recommended an approvable status to sitaxentan but said it would not yet approve the product. In July 2006, sitaxentan 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,
644:
Sitaxentan was approved for marketing in the
European Union in 2006, in Canada in 2006 and in Australia in 2007. By February 2008 it had been launched commercially in Germany, Austria, The Netherlands, the United Kingdom, Ireland, France, Spain and Italy.
929:
Barst RJ, Rich S, Widlitz A, Horn EM, McLaughlin V, McFarlin J (June 2002). "Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonist, in patients with pulmonary arterial hypertension: open-label pilot study".
1008:
1001:
1213:
649:
Encysive commenced a formal dispute resolution process in a preliminary meeting with the FDA. In
September 2007 the company announced that it was making preparations for another phase III
641:
On
December 10, 2010 Pfizer announced it would be withdrawing sitaxentan worldwide (both from marketing and from all clinical study use), citing that it is a cause of fatal liver damage.
653:(intended to be named STRIDE-5) to overcome the FDA's concerns. The takeover by Pfizer resulted in a reconfiguration and extension of these plans, to include combination therapy with
994:
109:
1206:
49:
544:
86:
530:
756:
Barst RJ, Langleben D, Frost A, Horn EM, Oudiz R, Shapiro S, et al. (February 2004). "Sitaxsentan therapy for pulmonary arterial hypertension".
1782:
1199:
1728:
629:
production and clearance of ET from circulation. In clinical trials, the efficacy of sitaxentan has been much the same as bosentan, but the
808:"Selective endothelin A receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease"
577:
purchased
Encysive in February 2008. In 2010, Pfizer voluntarily removed sitaxentan from the market due to concerns about liver toxicity.
876:
706:
986:
735:, a decreased dose of warfarin is needed when co-administered with sitaxentan. This is because warfarin acts to prevent blood from
566:
240:
139:
67:
904:"Sitaxentan for the oral treatment of pulmonary arterial hypertension: benefits from endothelin receptor subtype selectivity?"
1649:
1510:
1074:
606:
590:
1626:
877:"Encysive Pharmaceuticals to Conduct Phase III Study With Thelin (Sitaxsentan Sodium) in Pulmonary Arterial Hypertension"
1312:
610:
367:
1745:
1454:
427:
665:
81:
1807:
1265:
1130:
793:
1191:
855:
316:
1733:
1160:
97:
1701:
1772:
1653:
1018:
680:
614:
173:
416:
1797:
1787:
1777:
1426:
721:
307:
1683:
1403:
1370:
676:
204:
633:
of sitaxentan outweighs its benefits. Dosing is once daily, as opposed to twice daily for bosentan.
1802:
1792:
1617:
1244:
443:
260:
968:"Encysive Announces PDUFA Date for Thelin New Drug Application in Pulmonary Arterial Hypertension"
668:
observed with sitaxentan are class effects of endothelin receptor antagonists, and include :
1399:
1345:
806:
Girgis RE, Frost AE, Hill NS, Horn EM, Langleben D, McLaughlin VV, et al. (November 2007).
975:
947:
837:
773:
356:
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1226:
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915:
827:
819:
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701:
464:
269:
155:
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447:
1739:
1490:
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1107:
832:
807:
650:
630:
586:
59:
1766:
1586:
1500:
1411:
1239:
1222:
621:, a nonselective ET blocker, is negligible inhibition of the beneficial effects of ET
1671:
1594:
1480:
1416:
1350:
1330:
1230:
1064:
1049:
1035:
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1022:
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903:
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217:
53:
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20:
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1087:
1054:
736:
732:
716:
686:
618:
327:
336:
1170:
282:
28:
920:
739:, and if it remains unmetabolized, it can continue to thin the blood.
85:
574:
407:
222:
196:
192:
396:
691:
529:
520:
251:-(4-chloro-3-methyl-5-isoxazolyl)-2-acetyl]-3-thiophenesulfonamide
188:
856:"UPDATE 1-Encysive gets Canadian approval for hypertension drug"
601:) receptor selectively (by a factor of 6000 compared with the ET
387:
76:
1195:
990:
432:
879:. PrimeNewswire via COMTEX News Network. 29 September 2007
758:
American
Journal of Respiratory and Critical Care Medicine
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40:
35:
565:(TBC-11251) is a medication for the treatment of
552:Cc1cc2OCOc2cc1CC(=O)c3sccc3S(=O)(=O)Nc4onc(C)c4Cl
295:
976:"Primary or Unexplained Pulmonary Hypertension"
268:
1654:
1207:
1002:
8:
1587:Non-selective α-adrenergic receptor blockers
794:Citing liver damage, Pfizer withdraws Thelin
19:
1622:
1535:
1450:
1443:
1261:
1254:
1214:
1200:
1192:
1009:
995:
987:
617:. The rationale for benefit compared with
446:
355:
919:
831:
375:
789:
787:
748:
549:
442:
335:
245:
1017:Medications used in the management of
18:
796:, Associated Press, December 12, 2010
415:
58:
7:
121:
395:
286:
573:by Encysive Pharmaceuticals until
14:
707:upper respiratory tract infection
812:Annals of the Rheumatic Diseases
484:
481:
475:
27:
1783:Endothelin receptor antagonists
1650:Endothelin receptor antagonists
1511:Tyrosine hydroxylase inhibitors
1075:Endothelin receptor antagonists
1019:pulmonary arterial hypertension
908:Clinical Medicine: Therapeutics
605:). It is a sulfonamide class
567:pulmonary arterial hypertension
1659:Tooltip Pulmonary hypertension
1627:Serotonin receptor antagonists
607:endothelin receptor antagonist
496:
490:
469:
1:
1544:-Adrenergic receptor blockers
1313:Adrenergic release inhibitors
1270:-Adrenergic receptor agonists
1455:Monoamine oxidase inhibitors
727:Because sitaxentan inhibits
611:Food and Drug Administration
597:(ET) on the endothelin-A (ET
569:(PAH). It was marketed as
1824:
980:American Heart Association
613:(FDA) review for treating
459:Chemical and physical data
1723:
902:Mucke HA (January 2009).
770:10.1164/rccm.200307-957OC
675:abnormalities (increased
540:
274:210421-64-0 (sodium salt)
236:
26:
1161:Calcium channel blockers
944:10.1378/chest.121.6.1860
609:(ERA) and is undergoing
60:International Drug Names
824:10.1136/ard.2007.069609
1225:(and closely related)
858:. Reuters. 30 May 2007
615:pulmonary hypertension
1404:nicotinic antagonists
625:stimulation, such as
1371:Imidazoline receptor
87:by sitaxentan sodium
581:Mechanism of action
23:
1750:Never to phase III
1154:Adjunctive therapy
1760:
1759:
1719:
1718:
1611:
1610:
1607:
1606:
1603:
1602:
1527:
1526:
1435:
1434:
1400:Ganglion-blocking
1227:antihypertensives
1189:
1188:
921:10.4137/CMT.S2344
818:(11): 1467–1472.
637:Regulatory status
585:Sitaxentan is a
563:Sitaxentan sodium
560:
559:
531:Interactive image
428:CompTox Dashboard
227:Fecal (40 to 50%)
79:
16:Chemical compound
1815:
1660:
1656:
1623:
1536:
1451:
1444:
1262:
1255:
1249:vasoconstriction
1216:
1209:
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1011:
1004:
997:
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983:
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923:
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835:
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753:
702:nasal congestion
533:
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62:
31:
24:
22:
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1818:
1817:
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1812:
1808:Withdrawn drugs
1763:
1762:
1761:
1756:
1755:
1740:Clinical trials
1715:
1658:
1644:
1599:
1581:
1543:
1523:
1505:
1473:VMAT inhibitors
1467:
1431:
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1269:
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1234:
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1108:PDE5 inhibitors
1102:
1069:
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895:Further reading
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666:Adverse effects
663:
661:Adverse effects
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174:Protein binding
164:Bioavailability
156:Pharmacokinetic
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1491:Methoserpidine
1488:
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1240:Sympatholytics
1236:
1235:
1221:
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1211:
1204:
1196:
1187:
1186:
1184:
1183:
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1176:Oxygen therapy
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961:External links
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764:(4): 441–447.
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662:
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651:clinical trial
638:
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631:hepatotoxicity
622:
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593:the action of
587:small molecule
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1773:Benzodioxoles
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1501:Syrosingopine
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1412:Hexamethonium
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1223:Sympatholytic
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938:(6): 1860–8.
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444:DTXSID0057673
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39:
36:Clinical data
34:
30:
25:
1798:Sulfonamides
1788:Hepatotoxins
1778:Chloroarenes
1705:
1693:
1672:Aprocitentan
1667:
1595:Phentolamine
1481:Bietaserpine
1427:Trimethaphan
1417:Mecamylamine
1351:Guanethidine
1331:Debrisoquine
1245:α-adrenergic
1243:(antagonize
1097:
1065:Treprostinil
1050:Epoprostenol
1036:Prostacyclin
979:
970:. July 2005.
935:
931:
924:. CMT-S2344.
911:
907:
881:. Retrieved
871:
860:. Retrieved
850:
815:
811:
801:
761:
757:
751:
726:
697:constipation
673:liver enzyme
664:
647:
643:
640:
627:nitric oxide
584:
570:
562:
561:
417:ChEMBL282724
248:
205:Elimination
140:Legal status
134:Legal status
68:License data
1736:from market
1710:Sotatercept
1698:Ambrisentan
1618:antagonists
1486:Deserpidine
1422:Pentolinium
1385:Rilmenidine
1341:Guanazodine
1321:Bethanidine
1303:Tiamenidine
1293:Guanoxabenz
1133:stimulators
1083:Ambrisentan
914:: 111–121.
514: g·mol
270:184036-34-8
232:Identifiers
225:(50 to 60%)
41:Other names
1803:Thiophenes
1793:Isoxazoles
1767:Categories
1706:Sitaxentan
1702:+tadalafil
1684:+tadalafil
1680:Macitentan
1640:Lidanserin
1635:Ketanserin
1572:Trimazosin
1557:Ketanserin
1519:Metirosine
1440:Peripheral
1390:Tolonidine
1380:Moxonidine
1346:Guancydine
1298:Methyldopa
1288:Guanfacine
1145:Vericiguat
1116:Sildenafil
1098:Sitaxentan
1093:Macitentan
883:2007-12-12
862:2007-07-08
743:References
729:metabolism
655:sildenafil
595:endothelin
519:3D model (
507:Molar mass
377:J9QH779MEM
348:ChemSpider
308:IUPHAR/BPS
261:CAS Number
241:IUPAC name
199:-mediated)
184:Metabolism
168:70 to 100%
21:Sitaxentan
1746:Phase III
1734:Withdrawn
1694:selective
1688:Riociguat
1562:Indoramin
1552:Doxazosin
1496:Reserpine
1463:Pargyline
1356:Guanoclor
1336:Guanadrel
1326:Bretylium
1283:Guanabenz
1278:Clonidine
1166:Diuretics
1140:Riociguat
1121:Tadalafil
1060:Selexipag
1045:Beraprost
1038:analogues
712:dizziness
218:Excretion
207:half-life
147:Withdrawn
98:Routes of
54:Drugs.com
44:TBC-11251
1676:Bosentan
1577:Urapidil
1567:Prazosin
1447:Indirect
1373:agonists
1361:Guanoxan
1181:Warfarin
1088:Bosentan
1055:Iloprost
952:12065350
842:17472992
778:14630619
737:clotting
733:warfarin
722:flushing
717:insomnia
687:headache
619:bosentan
357:21106381
328:DrugBank
212:10 hours
110:ATC code
1258:Central
1171:Digoxin
833:2111639
465:Formula
337:DB06268
283:PubChem
189:Hepatic
178:>99%
126:)
120: (
118:C02KX03
84::
1729:WHO-EM
1616:Other
1532:Direct
950:
840:
830:
776:
591:blocks
575:Pfizer
571:Thelin
545:SMILES
512:454.90
408:ChEMBL
397:D07171
297:216235
197:CYP3A4
195:- and
193:CYP2C9
80:
1652:(for
932:Chest
692:edema
589:that
521:JSmol
223:Renal
1668:dual
948:PMID
838:PMID
774:PMID
679:and
388:KEGG
368:UNII
317:3950
158:data
104:Oral
50:AHFS
1704:),
1686:),
1231:C02
1131:sGC
1027:C02
1023:B01
940:doi
936:121
916:doi
828:PMC
820:doi
766:doi
762:169
731:of
681:AST
677:ALT
433:EPA
287:CID
123:WHO
82:EMA
1769::
1742::
1708:,
1678:,
1674:,
1655:PH
1025:,
978:.
946:.
934:.
910:.
906:.
836:.
826:.
816:66
814:.
810:.
786:^
772:.
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482:Cl
479:15
473:18
77:EU
1712:)
1700:(
1696:(
1690:)
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1670:(
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1542:1
1540:α
1402:/
1268:2
1266:α
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1201:v
1029:)
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996:v
982:.
954:.
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912:1
886:.
865:.
844:.
822::
780:.
768::
683:)
623:B
603:B
599:A
523:)
500:2
497:S
494:6
491:O
488:2
485:N
476:H
470:C
435:)
431:(
249:N
191:(
52:/
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