Identification

Name
Sitaxentan
Accession Number
DB06268
Type
Small Molecule
Groups
Approved, Investigational, Withdrawn
Description

Sitaxentan is a medication for the treatment of pulmonary arterial hypertension (PAH). It was marketed as Thelin by Encysive Pharmaceuticals until Pfizer purchased Encysive in February 2008. In 2010, Pfizer voluntarily removed sitaxentan from the market due to concerns about liver toxicity.

Structure
Thumb
Synonyms
  • Sitaxsentan
External IDs
IPI-1040 / TBC-11251
Product Ingredients
IngredientUNIICASInChI Key
Sitaxentan sodium6V9JH46E20210421-74-2MDTNUYUCUYPIHE-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ThelinTablet100 mgOralPfizer2007-06-192011-04-30Canada
Unapproved/Other Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ThelinTablet, film coated100 mgOralPfizer2006-08-10Not applicableEu
ThelinTablet, film coated100 mgOralPfizer2006-08-10Not applicableEu
ThelinTablet, film coated100 mgOralPfizer2006-08-10Not applicableEu
ThelinTablet, film coated100 mgOralPfizer2006-08-10Not applicableEu
ThelinTablet, film coated100 mgOralPfizer2006-08-10Not applicableEu
Categories
UNII
J9QH779MEM
CAS number
184036-34-8
Weight
Average: 454.905
Monoisotopic: 454.006005309
Chemical Formula
C18H15ClN2O6S2
InChI Key
PHWXUGHIIBDVKD-UHFFFAOYSA-N
InChI
InChI=1S/C18H15ClN2O6S2/c1-9-5-13-14(26-8-25-13)7-11(9)6-12(22)17-15(3-4-28-17)29(23,24)21-18-16(19)10(2)20-27-18/h3-5,7,21H,6,8H2,1-2H3
IUPAC Name
N-(4-chloro-3-methyl-1,2-oxazol-5-yl)-2-[2-(6-methyl-2H-1,3-benzodioxol-5-yl)acetyl]thiophene-3-sulfonamide
SMILES
CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)CC2=CC3=C(OCO3)C=C2C)=C1Cl

Pharmacology

Indication

Investigated for use/treatment in pulmonary hypertension, connective tissue diseases, hypertension, and congestive heart failure.

Structured Indications
Not Available
Pharmacodynamics

Sitaxentan belongs to a class of drugs known as endothelin receptor antagonists (ERAs). Patients with PAH have elevated levels of endothelin, a potent blood vessel constrictor, in their plasma and lung tissue. Sitaxentan blocks the binding of endothelin to its receptors, thereby negating endothelin's deleterious effects.

Mechanism of action

Sitaxentan is a competitive antagonist of endothelin-1 at the endothelin-A (ET-A) and endothelin-B (ET-B) receptors. Under normal conditions, endothelin-1 binding of ET-A or ET-B receptors causes pulmonary vasoconstriction. By blocking this interaction, Sitaxentan decreases pulmonary vascular resistance. Sitaxentan has a higher affinity for ET-A than ET-B.

TargetActionsOrganism
AEndothelin-1 receptor
antagonist
Human
UEndothelin B receptor
antagonist
Human
Absorption

70-100%

Volume of distribution
Not Available
Protein binding

99% +

Metabolism

Hepatic (CYP2C9- and CYP3A4-mediated)

Route of elimination

Renal (50 to 60%) Fecal (40 to 50%)

Half life

10 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypotensive activities of Sitaxentan.Experimental
AbirateroneThe metabolism of Sitaxentan can be decreased when combined with Abiraterone.Approved
AcebutololAcebutolol may increase the hypotensive activities of Sitaxentan.Approved
AlfuzosinAlfuzosin may increase the hypotensive activities of Sitaxentan.Approved, Investigational
AliskirenAliskiren may increase the hypotensive activities of Sitaxentan.Approved, Investigational
AlprenololAlprenolol may increase the hypotensive activities of Sitaxentan.Approved, Withdrawn
AmbrisentanSitaxentan may increase the hypotensive activities of Ambrisentan.Approved, Investigational
AmifostineSitaxentan may increase the hypotensive activities of Amifostine.Approved, Investigational
AmiodaroneThe metabolism of Sitaxentan can be decreased when combined with Amiodarone.Approved, Investigational
AmlodipineAmlodipine may increase the hypotensive activities of Sitaxentan.Approved
AprepitantThe metabolism of Sitaxentan can be increased when combined with Aprepitant.Approved, Investigational
AtenololAtenolol may increase the hypotensive activities of Sitaxentan.Approved
AtorvastatinThe risk or severity of adverse effects can be increased when Sitaxentan is combined with Atorvastatin.Approved
BenazeprilBenazepril may increase the hypotensive activities of Sitaxentan.Approved, Investigational
BendroflumethiazideBendroflumethiazide may increase the hypotensive activities of Sitaxentan.Approved
BenmoxinBenmoxin may increase the hypotensive activities of Sitaxentan.Withdrawn
BepridilBepridil may increase the hypotensive activities of Sitaxentan.Approved, Withdrawn
BetaxololBetaxolol may increase the hypotensive activities of Sitaxentan.Approved
BethanidineBethanidine may increase the hypotensive activities of Sitaxentan.Approved
BietaserpineBietaserpine may increase the hypotensive activities of Sitaxentan.Experimental
BimatoprostBimatoprost may increase the hypotensive activities of Sitaxentan.Approved, Investigational
BisoprololBisoprolol may increase the hypotensive activities of Sitaxentan.Approved
BosentanBosentan may increase the hypotensive activities of Sitaxentan.Approved, Investigational
BQ-123BQ-123 may increase the hypotensive activities of Sitaxentan.Investigational
BretyliumBretylium may increase the hypotensive activities of Sitaxentan.Approved
BrimonidineBrimonidine may increase the antihypertensive activities of Sitaxentan.Approved
BrofaromineBrofaromine may increase the hypotensive activities of Sitaxentan.Experimental
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with Sitaxentan.Approved, Investigational
BupranololBupranolol may increase the hypotensive activities of Sitaxentan.Approved
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Sitaxentan.Approved
CadralazineCadralazine may increase the hypotensive activities of Sitaxentan.Experimental
CafedrineCafedrine may increase the hypotensive activities of Sitaxentan.Investigational
Candesartan cilexetilCandesartan may increase the hypotensive activities of Sitaxentan.Approved
CandoxatrilCandoxatril may increase the hypotensive activities of Sitaxentan.Experimental
CapecitabineThe metabolism of Sitaxentan can be decreased when combined with Capecitabine.Approved, Investigational
CaptoprilCaptopril may increase the hypotensive activities of Sitaxentan.Approved
CarbamazepineThe metabolism of Sitaxentan can be increased when combined with Carbamazepine.Approved, Investigational
CaroxazoneCaroxazone may increase the hypotensive activities of Sitaxentan.Withdrawn
CarteololCarteolol may increase the hypotensive activities of Sitaxentan.Approved
CarvedilolCarvedilol may increase the hypotensive activities of Sitaxentan.Approved, Investigational
CeliprololCeliprolol may increase the hypotensive activities of Sitaxentan.Approved, Investigational
CeritinibThe serum concentration of Sitaxentan can be increased when it is combined with Ceritinib.Approved
CerivastatinThe serum concentration of Cerivastatin can be increased when it is combined with Sitaxentan.Withdrawn
ChlorothiazideChlorothiazide may increase the hypotensive activities of Sitaxentan.Approved, Vet Approved
ChlorthalidoneChlorthalidone may increase the hypotensive activities of Sitaxentan.Approved
CholecalciferolThe metabolism of Sitaxentan can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CicletanineCicletanine may increase the hypotensive activities of Sitaxentan.Investigational
CilazaprilCilazapril may increase the hypotensive activities of Sitaxentan.Approved
CilostazolThe serum concentration of Cilostazol can be increased when it is combined with Sitaxentan.Approved
ClonidineClonidine may increase the hypotensive activities of Sitaxentan.Approved
CloranololCloranolol may increase the hypotensive activities of Sitaxentan.Experimental
ClotrimazoleThe metabolism of Sitaxentan can be decreased when combined with Clotrimazole.Approved, Vet Approved
CrisaboroleThe metabolism of Sitaxentan can be decreased when combined with Crisaborole.Approved
CryptenamineCryptenamine may increase the hypotensive activities of Sitaxentan.Approved
CyclopenthiazideCyclopenthiazide may increase the hypotensive activities of Sitaxentan.Experimental
CyclosporineThe serum concentration of Sitaxentan can be increased when it is combined with Cyclosporine.Approved, Investigational, Vet Approved
CyclothiazideCyclothiazide may increase the hypotensive activities of Sitaxentan.Approved
DabrafenibThe serum concentration of Sitaxentan can be decreased when it is combined with Dabrafenib.Approved
DebrisoquinDebrisoquin may increase the hypotensive activities of Sitaxentan.Approved, Investigational
DelaprilDelapril may increase the hypotensive activities of Sitaxentan.Experimental
DelavirdineThe metabolism of Sitaxentan can be decreased when combined with Delavirdine.Approved
DeserpidineDeserpidine may increase the hypotensive activities of Sitaxentan.Approved
DiazoxideDiazoxide may increase the hypotensive activities of Sitaxentan.Approved
diethylnorsperminediethylnorspermine may increase the hypotensive activities of Sitaxentan.Investigational
DihydralazineDihydralazine may increase the hypotensive activities of Sitaxentan.Investigational
DihydroergocornineThe risk or severity of adverse effects can be increased when Dihydroergocornine is combined with Sitaxentan.Approved
DihydroergocristineThe risk or severity of adverse effects can be increased when Dihydroergocristine is combined with Sitaxentan.Experimental
DihydroergocryptineThe risk or severity of adverse effects can be increased when Dihydroergocryptine is combined with Sitaxentan.Experimental
DihydroergotamineThe risk or severity of adverse effects can be increased when Dihydroergotamine is combined with Sitaxentan.Approved
DiltiazemDiltiazem may increase the hypotensive activities of Sitaxentan.Approved
DorzolamideDorzolamide may increase the hypotensive activities of Sitaxentan.Approved
DosulepinThe metabolism of Sitaxentan can be decreased when combined with Dosulepin.Approved
DoxazosinDoxazosin may increase the hypotensive activities of Sitaxentan.Approved
EfavirenzThe metabolism of Sitaxentan can be decreased when combined with Efavirenz.Approved, Investigational
EfonidipineEfonidipine may increase the hypotensive activities of Sitaxentan.Approved
EnalaprilEnalapril may increase the hypotensive activities of Sitaxentan.Approved, Vet Approved
EnalaprilatEnalaprilat may increase the hypotensive activities of Sitaxentan.Approved
EndralazineEndralazine may increase the hypotensive activities of Sitaxentan.Experimental
EpanololEpanolol may increase the hypotensive activities of Sitaxentan.Experimental
EpoprostenolEpoprostenol may increase the hypotensive activities of Sitaxentan.Approved
EprosartanEprosartan may increase the hypotensive activities of Sitaxentan.Approved
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Sitaxentan.Approved
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Sitaxentan.Approved
EtravirineThe metabolism of Sitaxentan can be decreased when combined with Etravirine.Approved
FelodipineFelodipine may increase the hypotensive activities of Sitaxentan.Approved, Investigational
FenoldopamFenoldopam may increase the hypotensive activities of Sitaxentan.Approved
Ferulic acidFerulic acid may increase the hypotensive activities of Sitaxentan.Experimental
FloxuridineThe metabolism of Sitaxentan can be decreased when combined with Floxuridine.Approved
FluconazoleThe metabolism of Sitaxentan can be decreased when combined with Fluconazole.Approved
FluorouracilThe metabolism of Sitaxentan can be decreased when combined with Fluorouracil.Approved
FluvastatinThe metabolism of Sitaxentan can be decreased when combined with Fluvastatin.Approved
FluvoxamineThe metabolism of Sitaxentan can be decreased when combined with Fluvoxamine.Approved, Investigational
FosinoprilFosinopril may increase the hypotensive activities of Sitaxentan.Approved
FosphenytoinThe metabolism of Sitaxentan can be increased when combined with Fosphenytoin.Approved
FurazolidoneFurazolidone may increase the hypotensive activities of Sitaxentan.Approved, Investigational, Vet Approved
GemfibrozilThe metabolism of Sitaxentan can be decreased when combined with Gemfibrozil.Approved
GuanabenzGuanabenz may increase the hypotensive activities of Sitaxentan.Approved, Investigational
GuanadrelGuanadrel may increase the hypotensive activities of Sitaxentan.Approved
GuanazodineSitaxentan may increase the hypotensive activities of Guanazodine.Experimental
GuanethidineGuanethidine may increase the hypotensive activities of Sitaxentan.Approved
GuanfacineGuanfacine may increase the hypotensive activities of Sitaxentan.Approved, Investigational
GuanoclorSitaxentan may increase the hypotensive activities of Guanoclor.Experimental
GuanoxabenzSitaxentan may increase the hypotensive activities of Guanoxabenz.Experimental
GuanoxanSitaxentan may increase the hypotensive activities of Guanoxan.Experimental
HarmalineHarmaline may increase the hypotensive activities of Sitaxentan.Experimental
HexamethoniumHexamethonium may increase the hypotensive activities of Sitaxentan.Experimental
HydracarbazineHydracarbazine may increase the hypotensive activities of Sitaxentan.Experimental
HydralazineHydralazine may increase the hypotensive activities of Sitaxentan.Approved
HydrochlorothiazideHydrochlorothiazide may increase the hypotensive activities of Sitaxentan.Approved, Vet Approved
HydroflumethiazideHydroflumethiazide may increase the hypotensive activities of Sitaxentan.Approved, Investigational
IloprostIloprost may increase the hypotensive activities of Sitaxentan.Approved, Investigational
ImidaprilImidapril may increase the hypotensive activities of Sitaxentan.Investigational
IndapamideIndapamide may increase the hypotensive activities of Sitaxentan.Approved
IndenololIndenolol may increase the hypotensive activities of Sitaxentan.Withdrawn
IndinavirThe metabolism of Sitaxentan can be decreased when combined with Indinavir.Approved
IndoraminIndoramin may increase the hypotensive activities of Sitaxentan.Withdrawn
IproclozideIproclozide may increase the hypotensive activities of Sitaxentan.Withdrawn
IproniazidIproniazid may increase the hypotensive activities of Sitaxentan.Withdrawn
IrbesartanThe metabolism of Sitaxentan can be decreased when combined with Irbesartan.Approved, Investigational
IsocarboxazidIsocarboxazid may increase the hypotensive activities of Sitaxentan.Approved
IsradipineIsradipine may increase the hypotensive activities of Sitaxentan.Approved
KetanserinKetanserin may increase the hypotensive activities of Sitaxentan.Investigational
KetoconazoleThe metabolism of Sitaxentan can be decreased when combined with Ketoconazole.Approved, Investigational
LabetalolLabetalol may increase the hypotensive activities of Sitaxentan.Approved
LacidipineLacidipine may increase the hypotensive activities of Sitaxentan.Approved, Investigational
LatanoprostLatanoprost may increase the hypotensive activities of Sitaxentan.Approved, Investigational
LeflunomideThe metabolism of Sitaxentan can be decreased when combined with Leflunomide.Approved, Investigational
LercanidipineLercanidipine may increase the hypotensive activities of Sitaxentan.Approved, Investigational
LinsidomineLinsidomine may increase the hypotensive activities of Sitaxentan.Experimental
LisinoprilLisinopril may increase the hypotensive activities of Sitaxentan.Approved, Investigational
LisurideThe risk or severity of adverse effects can be increased when Lisuride is combined with Sitaxentan.Approved, Investigational
LobeglitazoneThe metabolism of Sitaxentan can be decreased when combined with Lobeglitazone.Approved, Investigational
LofexidineLofexidine may increase the hypotensive activities of Sitaxentan.Approved, Investigational
LosartanThe metabolism of Sitaxentan can be decreased when combined with Losartan.Approved
LovastatinThe metabolism of Sitaxentan can be decreased when combined with Lovastatin.Approved, Investigational
LumacaftorThe serum concentration of Sitaxentan can be decreased when it is combined with Lumacaftor.Approved
Lysergic Acid DiethylamideThe risk or severity of adverse effects can be increased when Lysergic Acid Diethylamide is combined with Sitaxentan.Illicit, Investigational, Withdrawn
MacitentanSitaxentan may increase the hypotensive activities of Macitentan.Approved
ManidipineManidipine may increase the hypotensive activities of Sitaxentan.Approved, Investigational
MebanazineMebanazine may increase the hypotensive activities of Sitaxentan.Withdrawn
MecamylamineMecamylamine may increase the hypotensive activities of Sitaxentan.Approved
MetergolineThe risk or severity of adverse effects can be increased when Metergoline is combined with Sitaxentan.Experimental
MethoserpidineSitaxentan may increase the hypotensive activities of Methoserpidine.Experimental
MethyldopaMethyldopa may increase the hypotensive activities of Sitaxentan.Approved
Methylene blueMethylene blue may increase the hypotensive activities of Sitaxentan.Approved, Investigational
MethylergometrineThe risk or severity of adverse effects can be increased when Methylergometrine is combined with Sitaxentan.Approved
MethylphenidateMethylphenidate may decrease the antihypertensive activities of Sitaxentan.Approved, Investigational
MethysergideThe risk or severity of adverse effects can be increased when Methysergide is combined with Sitaxentan.Approved
MetipranololMetipranolol may increase the hypotensive activities of Sitaxentan.Approved
MetolazoneMetolazone may increase the hypotensive activities of Sitaxentan.Approved
MetoprololMetoprolol may increase the hypotensive activities of Sitaxentan.Approved, Investigational
MetyrosineMetyrosine may increase the hypotensive activities of Sitaxentan.Approved
MevastatinThe serum concentration of Mevastatin can be increased when it is combined with Sitaxentan.Experimental
MibefradilMibefradil may increase the hypotensive activities of Sitaxentan.Investigational, Withdrawn
MidostaurinThe metabolism of Sitaxentan can be decreased when combined with Midostaurin.Approved
MifepristoneThe serum concentration of Sitaxentan can be increased when it is combined with Mifepristone.Approved, Investigational
MinaprineMinaprine may increase the hypotensive activities of Sitaxentan.Approved
MinoxidilMinoxidil may increase the hypotensive activities of Sitaxentan.Approved
MirodenafilMirodenafil may increase the antihypertensive activities of Sitaxentan.Investigational
MoclobemideMoclobemide may increase the hypotensive activities of Sitaxentan.Approved
MoexiprilMoexipril may increase the hypotensive activities of Sitaxentan.Approved
MolsidomineMolsidomine may increase the hypotensive activities of Sitaxentan.Approved, Investigational
MoxonidineMoxonidine may increase the hypotensive activities of Sitaxentan.Approved, Investigational
MuzolimineMuzolimine may increase the hypotensive activities of Sitaxentan.Experimental
NadololNadolol may increase the hypotensive activities of Sitaxentan.Approved
NaftopidilNaftopidil may increase the hypotensive activities of Sitaxentan.Investigational
NebivololNebivolol may increase the hypotensive activities of Sitaxentan.Approved, Investigational
NialamideNialamide may increase the hypotensive activities of Sitaxentan.Withdrawn
NicardipineThe metabolism of Sitaxentan can be decreased when combined with Nicardipine.Approved
NicergolineThe risk or severity of adverse effects can be increased when Nicergoline is combined with Sitaxentan.Approved, Investigational
NicorandilNicorandil may increase the hypotensive activities of Sitaxentan.Approved, Investigational
NiguldipineNiguldipine may increase the hypotensive activities of Sitaxentan.Experimental
NilvadipineNilvadipine may increase the hypotensive activities of Sitaxentan.Approved, Investigational
NimodipineNimodipine may increase the hypotensive activities of Sitaxentan.Approved
NisoldipineNisoldipine may increase the hypotensive activities of Sitaxentan.Approved
NitrendipineNitrendipine may increase the hypotensive activities of Sitaxentan.Approved, Investigational
NitroprussideNitroprusside may increase the hypotensive activities of Sitaxentan.Approved
ObinutuzumabSitaxentan may increase the hypotensive activities of Obinutuzumab.Approved
OctamoxinOctamoxin may increase the hypotensive activities of Sitaxentan.Withdrawn
OlmesartanOlmesartan may increase the hypotensive activities of Sitaxentan.Approved, Investigational
OmapatrilatOmapatrilat may increase the hypotensive activities of Sitaxentan.Investigational
OmeprazoleThe metabolism of Sitaxentan can be decreased when combined with Omeprazole.Approved, Investigational, Vet Approved
OxprenololOxprenolol may increase the hypotensive activities of Sitaxentan.Approved
PargylinePargyline may increase the hypotensive activities of Sitaxentan.Approved
PenbutololPenbutolol may increase the hypotensive activities of Sitaxentan.Approved, Investigational
PentoliniumPentolinium may increase the hypotensive activities of Sitaxentan.Approved
PentoxifyllinePentoxifylline may increase the hypotensive activities of Sitaxentan.Approved, Investigational
PergolideThe risk or severity of adverse effects can be increased when Pergolide is combined with Sitaxentan.Approved, Investigational, Vet Approved, Withdrawn
PerindoprilPerindopril may increase the hypotensive activities of Sitaxentan.Approved
PhenelzinePhenelzine may increase the hypotensive activities of Sitaxentan.Approved
PheniprazinePheniprazine may increase the hypotensive activities of Sitaxentan.Withdrawn
PhenobarbitalThe metabolism of Sitaxentan can be increased when combined with Phenobarbital.Approved
PhenoxybenzaminePhenoxybenzamine may increase the hypotensive activities of Sitaxentan.Approved
PhenoxypropazinePhenoxypropazine may increase the hypotensive activities of Sitaxentan.Withdrawn
PhentolaminePhentolamine may increase the hypotensive activities of Sitaxentan.Approved
PhenytoinThe metabolism of Sitaxentan can be increased when combined with Phenytoin.Approved, Vet Approved
PinacidilPinacidil may increase the hypotensive activities of Sitaxentan.Withdrawn
PindololPindolol may increase the hypotensive activities of Sitaxentan.Approved
PirlindolePirlindole may increase the hypotensive activities of Sitaxentan.Approved
PitavastatinThe serum concentration of Pitavastatin can be increased when it is combined with Sitaxentan.Approved
PivhydrazinePivhydrazine may increase the hypotensive activities of Sitaxentan.Withdrawn
PolythiazidePolythiazide may increase the hypotensive activities of Sitaxentan.Approved
PravastatinThe serum concentration of Pravastatin can be increased when it is combined with Sitaxentan.Approved
PrazosinPrazosin may increase the hypotensive activities of Sitaxentan.Approved
PrimidoneThe metabolism of Sitaxentan can be increased when combined with Primidone.Approved, Vet Approved
PropranololPropranolol may increase the hypotensive activities of Sitaxentan.Approved, Investigational
PyrimethamineThe metabolism of Sitaxentan can be decreased when combined with Pyrimethamine.Approved, Vet Approved
QuinaprilQuinapril may increase the hypotensive activities of Sitaxentan.Approved, Investigational
QuinineQuinine may increase the hypotensive activities of Sitaxentan.Approved
RamiprilRamipril may increase the hypotensive activities of Sitaxentan.Approved
RasagilineRasagiline may increase the hypotensive activities of Sitaxentan.Approved
RemikirenRemikiren may increase the hypotensive activities of Sitaxentan.Approved
RescinnamineRescinnamine may increase the hypotensive activities of Sitaxentan.Approved
ReserpineReserpine may increase the hypotensive activities of Sitaxentan.Approved, Investigational
RifampicinThe metabolism of Sitaxentan can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Sitaxentan can be increased when combined with Rifapentine.Approved
RilmenidineRilmenidine may increase the hypotensive activities of Sitaxentan.Investigational
RiociguatSitaxentan may increase the hypotensive activities of Riociguat.Approved
RituximabSitaxentan may increase the hypotensive activities of Rituximab.Approved
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Sitaxentan.Approved
SafrazineSafrazine may increase the hypotensive activities of Sitaxentan.Withdrawn
SaprisartanSaprisartan may increase the hypotensive activities of Sitaxentan.Experimental
SecobarbitalThe metabolism of Sitaxentan can be increased when combined with Secobarbital.Approved, Vet Approved
SelegilineSelegiline may increase the hypotensive activities of Sitaxentan.Approved, Investigational, Vet Approved
SelexipagSelexipag may increase the hypotensive activities of Sitaxentan.Approved
SildenafilSildenafil may increase the antihypertensive activities of Sitaxentan.Approved, Investigational
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Sitaxentan.Approved
SorafenibThe metabolism of Sitaxentan can be decreased when combined with Sorafenib.Approved, Investigational
SpiraprilSpirapril may increase the hypotensive activities of Sitaxentan.Approved
SulfadiazineThe metabolism of Sitaxentan can be decreased when combined with Sulfadiazine.Approved, Vet Approved
SulfamethoxazoleThe metabolism of Sitaxentan can be decreased when combined with Sulfamethoxazole.Approved
SulfisoxazoleThe metabolism of Sitaxentan can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TadalafilTadalafil may increase the antihypertensive activities of Sitaxentan.Approved, Investigational
TalinololTalinolol may increase the hypotensive activities of Sitaxentan.Investigational
TelmisartanTelmisartan may increase the hypotensive activities of Sitaxentan.Approved, Investigational
TemocaprilTemocapril may increase the hypotensive activities of Sitaxentan.Experimental, Investigational
TergurideThe risk or severity of adverse effects can be increased when Terguride is combined with Sitaxentan.Experimental
TerlipressinTerlipressin may increase the hypotensive activities of Sitaxentan.Approved, Investigational
TetrahydropalmatineTetrahydropalmatine may increase the hypotensive activities of Sitaxentan.Investigational
TheodrenalineTheodrenaline may increase the hypotensive activities of Sitaxentan.Investigational
TiboloneTibolone may increase the hypotensive activities of Sitaxentan.Approved, Investigational
TicagrelorThe metabolism of Sitaxentan can be decreased when combined with Ticagrelor.Approved
TiclopidineThe metabolism of Sitaxentan can be decreased when combined with Ticlopidine.Approved
TicrynafenTicrynafen may increase the hypotensive activities of Sitaxentan.Withdrawn
TimololTimolol may increase the hypotensive activities of Sitaxentan.Approved
TofacitinibThe serum concentration of Tofacitinib can be increased when it is combined with Sitaxentan.Approved, Investigational
TolazolineTolazoline may increase the hypotensive activities of Sitaxentan.Approved, Vet Approved
TolbutamideThe metabolism of Sitaxentan can be decreased when combined with Tolbutamide.Approved
TolonidineSitaxentan may increase the hypotensive activities of Tolonidine.Experimental
ToloxatoneToloxatone may increase the hypotensive activities of Sitaxentan.Approved
TopiroxostatThe metabolism of Sitaxentan can be decreased when combined with Topiroxostat.Approved, Investigational
TorasemideTorasemide may increase the hypotensive activities of Sitaxentan.Approved
TrandolaprilTrandolapril may increase the hypotensive activities of Sitaxentan.Approved
Trans-2-PhenylcyclopropylamineTrans-2-Phenylcyclopropylamine may increase the hypotensive activities of Sitaxentan.Experimental
TranylcypromineTranylcypromine may increase the hypotensive activities of Sitaxentan.Approved
TravoprostTravoprost may increase the hypotensive activities of Sitaxentan.Approved
TreprostinilTreprostinil may increase the hypotensive activities of Sitaxentan.Approved, Investigational
TrichlormethiazideTrichlormethiazide may increase the hypotensive activities of Sitaxentan.Approved, Vet Approved
TrimazosinTrimazosin may increase the hypotensive activities of Sitaxentan.Experimental
TrimethaphanTrimethaphan may increase the hypotensive activities of Sitaxentan.Approved, Investigational
TrimethoprimThe metabolism of Sitaxentan can be decreased when combined with Trimethoprim.Approved, Vet Approved
UbidecarenoneThe serum concentration of Ubidecarenone can be increased when it is combined with Sitaxentan.Approved, Experimental
UdenafilUdenafil may increase the antihypertensive activities of Sitaxentan.Approved, Investigational
UnoprostoneUnoprostone may increase the hypotensive activities of Sitaxentan.Approved
UrapidilUrapidil may increase the hypotensive activities of Sitaxentan.Investigational
Valproic AcidThe metabolism of Sitaxentan can be decreased when combined with Valproic Acid.Approved, Investigational
ValsartanThe metabolism of Sitaxentan can be decreased when combined with Valsartan.Approved, Investigational
VardenafilVardenafil may increase the antihypertensive activities of Sitaxentan.Approved
VincamineVincamine may increase the hypotensive activities of Sitaxentan.Experimental
VinpocetineVinpocetine may increase the hypotensive activities of Sitaxentan.Investigational
VoriconazoleThe metabolism of Sitaxentan can be decreased when combined with Voriconazole.Approved, Investigational
WarfarinThe serum concentration of Warfarin can be increased when it is combined with Sitaxentan.Approved
XipamideXipamide may increase the hypotensive activities of Sitaxentan.Experimental
XylometazolineXylometazoline may increase the hypotensive activities of Sitaxentan.Approved
YohimbineYohimbine may decrease the antihypertensive activities of Sitaxentan.Approved, Vet Approved
ZafirlukastThe metabolism of Sitaxentan can be decreased when combined with Zafirlukast.Approved, Investigational
ZofenoprilZofenopril may increase the hypotensive activities of Sitaxentan.Experimental
Food Interactions
  • Take without regard to meals

References

General References
Not Available
External Links
Human Metabolome Database
HMDB15629
KEGG Drug
D07171
PubChem Compound
216235
PubChem Substance
99443241
ChemSpider
187436
BindingDB
50058126
ChEBI
135736
ChEMBL
CHEMBL282724
PharmGKB
PA165958361
IUPHAR
3950
Guide to Pharmacology
GtP Drug Page
Wikipedia
Sitaxentan
ATC Codes
C02KX03 — Sitaxentan

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedBasic SciencePulmonary Arterial Hypertension (PAH) / Vasoconstriction / Vasodilation1
1CompletedTreatmentHealthy Volunteers1
1TerminatedTreatmentPulmonary Arterial Hypertension (PAH)1
1WithdrawnBasic SciencePulmonary Arterial Hypertension (PAH)2
2CompletedTreatmentChronic Kidney Disease (CKD) / CRD1
2CompletedTreatmentCardiac Surgery Subjects / Subjects Undergoing CABG and/or Cardiac Valve Replacement1
2CompletedTreatmentDiastolic Heart Failure1
2TerminatedTreatmentEffect of Sitaxsentan on Airway Remodeling in Severe Asthma1
2Unknown StatusTreatmentBlood Pressures / Chronic Kidney Disease (CKD) / Proteinuria1
2, 3Unknown StatusTreatmentPulmonary Hypertension (PH)1
3CompletedTreatmentPulmonary Hypertension (PH)1
3TerminatedNot AvailablePulmonary Arterial Hypertension (PAH)1
3TerminatedTreatmentPulmonary Arterial Hypertension (PAH) / Pulmonary Hypertension (PH)3
3TerminatedTreatmentPulmonary Hypertension (PH)2
Not AvailableCompletedNot AvailablePulmonary Arterial Hypertension (PAH)1
Not AvailableCompletedOtherHeart Diseases1
Not AvailableTerminatedNot AvailablePulmonary Arterial Hypertension (PAH)1
Not AvailableUnknown StatusNot AvailablePAH WHO Group I / Pulmonary Arterial Hypertension (PAH) / Pulmonary Hypertension (PH)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral100 mg
Tablet, film coatedOral100 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2281090No2005-06-072018-04-02Canada
CA2161346No2004-11-232014-05-20Canada

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0181 mg/mLALOGPS
logP3.35ALOGPS
logP3.09ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)6.89ChemAxon
pKa (Strongest Basic)0.75ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area107.73 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity105.8 m3·mol-1ChemAxon
Polarizability43.12 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9811
Blood Brain Barrier+0.511
Caco-2 permeable-0.5662
P-glycoprotein substrateNon-substrate0.8285
P-glycoprotein inhibitor INon-inhibitor0.8519
P-glycoprotein inhibitor IINon-inhibitor0.8682
Renal organic cation transporterNon-inhibitor0.9158
CYP450 2C9 substrateNon-substrate0.8057
CYP450 2D6 substrateNon-substrate0.8266
CYP450 3A4 substrateNon-substrate0.5263
CYP450 1A2 substrateNon-inhibitor0.6693
CYP450 2C9 inhibitorInhibitor0.7225
CYP450 2D6 inhibitorNon-inhibitor0.8052
CYP450 2C19 inhibitorNon-inhibitor0.5
CYP450 3A4 inhibitorInhibitor0.925
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9157
Ames testNon AMES toxic0.634
CarcinogenicityNon-carcinogens0.5575
BiodegradationNot ready biodegradable0.9958
Rat acute toxicity2.5528 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9901
hERG inhibition (predictor II)Non-inhibitor0.9051
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzodioxoles. These are organic compounds containing a benzene ring fused to either isomers of dioxole. Dioxole is a five-membered unsaturated ring of two oxygen atoms and three carbon atoms.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzodioxoles
Sub Class
Not Available
Direct Parent
Benzodioxoles
Alternative Parents
Aryl alkyl ketones / Organosulfonamides / Aryl chlorides / Benzenoids / Thiophenes / Aminosulfonyl compounds / Heteroaromatic compounds / Isoxazoles / Acetals / Oxacyclic compounds
show 6 more
Substituents
Benzodioxole / Aryl alkyl ketone / Aryl ketone / Aryl chloride / Aryl halide / Benzenoid / Organosulfonic acid amide / Azole / Isoxazole / Heteroaromatic compound
show 20 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Details
1. Endothelin-1 receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
Receptor for endothelin-1. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of binding affinities for ET-A is:...
Gene Name
EDNRA
Uniprot ID
P25101
Uniprot Name
Endothelin-1 receptor
Molecular Weight
48721.76 Da
References
  1. Girgis RE, Frost AE, Hill NS, Horn EM, Langleben D, McLaughlin VV, Oudiz RJ, Robbins IM, Seibold JR, Shapiro S, Tapson VF, Barst RJ: Selective endothelin A receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease. Ann Rheum Dis. 2007 Nov;66(11):1467-72. Epub 2007 May 1. [PubMed:17472992]
  2. Albertini M, Lafortuna CL, Ciminaghi B, Mazzola S, Clement MG: Endothelin involvement in respiratory centre activity. Prostaglandins Leukot Essent Fatty Acids. 2001 Sep;65(3):157-63. [PubMed:11728166]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  4. Kiowski W, Sutsch G, Oechslin E, Bertel O: Hemodynamic effects of bosentan in patients with chronic heart failure. Heart Fail Rev. 2001 Dec;6(4):325-34. [PubMed:11447307]
  5. Kramp R, Fourmanoir P, Caron N: Endothelin resets renal blood flow autoregulatory efficiency during acute blockade of NO in the rat. Am J Physiol Renal Physiol. 2001 Dec;281(6):F1132-40. [PubMed:11704565]
  6. Martin C, Held HD, Uhlig S: Differential effects of the mixed ET(A)/ET(B)-receptor antagonist bosentan on endothelin-induced bronchoconstriction, vasoconstriction and prostacyclin release. Naunyn Schmiedebergs Arch Pharmacol. 2000 Aug;362(2):128-36. [PubMed:10961375]
  7. Sihvola RK, Pulkkinen VP, Koskinen PK, Lemstrom KB: Crosstalk of endothelin-1 and platelet-derived growth factor in cardiac allograft arteriosclerosis. J Am Coll Cardiol. 2002 Feb 20;39(4):710-7. [PubMed:11849873]
Details
2. Endothelin B receptor
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Peptide hormone binding
Specific Function
Non-specific receptor for endothelin 1, 2, and 3. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
Gene Name
EDNRB
Uniprot ID
P24530
Uniprot Name
Endothelin B receptor
Molecular Weight
49643.255 Da
References
  1. Girgis RE, Frost AE, Hill NS, Horn EM, Langleben D, McLaughlin VV, Oudiz RJ, Robbins IM, Seibold JR, Shapiro S, Tapson VF, Barst RJ: Selective endothelin A receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease. Ann Rheum Dis. 2007 Nov;66(11):1467-72. Epub 2007 May 1. [PubMed:17472992]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  3. Gardiner SM, Kemp PA, March JE, Bennett T: Effects of bosentan (Ro 47-0203), an ETA-, ETB-receptor antagonist, on regional haemodynamic responses to endothelins in conscious rats. Br J Pharmacol. 1994 Jul;112(3):823-30. [PubMed:7921608]
  4. Gupta SK, Saxena A, Singh U, Arya DS: Bosentan, the mixed ETA-ETB endothelin receptor antagonist, attenuated oxidative stress after experimental myocardial ischemia and reperfusion. Mol Cell Biochem. 2005 Jul;275(1-2):67-74. [PubMed:16335785]
  5. Marano G, Palazzesi S, Bernucci P, Grigioni M, Formigari R, Ballerini L: ET(A)/ET(B) receptor antagonist bosentan inhibits neointimal development in collared carotid arteries of rabbits. Life Sci. 1998;63(18):PL259-66. [PubMed:9806221]
  6. Richard V, Kaeffer N, Hogie M, Tron C, Blanc T, Thuillez C: Role of endogenous endothelin in myocardial and coronary endothelial injury after ischaemia and reperfusion in rats: studies with bosentan, a mixed ETA-ETB antagonist. Br J Pharmacol. 1994 Nov;113(3):869-76. [PubMed:7858879]
  7. Said SA, Ammar el SM, Suddek GM: Effect of bosentan (ETA/ETB receptor antagonist) on metabolic changes during stress and diabetes. Pharmacol Res. 2005 Feb;51(2):107-15. [PubMed:15629255]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Barst RJ, Rich S, Widlitz A, Horn EM, McLaughlin V, McFarlin J: Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonist, in patients with pulmonary arterial hypertension: open-label pilot study. Chest. 2002 Jun;121(6):1860-8. [PubMed:12065350]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Pulido T, Sandoval J, Roquet I, Gutierrez R, Rueda T, Pena H, Santos E, Miranda MT, Lupi E: Interaction of acenocoumarol and sitaxentan in pulmonary arterial hypertension. Eur J Clin Invest. 2009 Jun;39 Suppl 2:14-8. doi: 10.1111/j.1365-2362.2009.02116.x. [PubMed:19335742]
  2. Opitz CF, Ewert R, Kirch W, Pittrow D: Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter? Eur Heart J. 2008 Aug;29(16):1936-48. doi: 10.1093/eurheartj/ehn234. Epub 2008 Jun 17. [PubMed:18562303]
  3. Barst RJ, Rich S, Widlitz A, Horn EM, McLaughlin V, McFarlin J: Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonist, in patients with pulmonary arterial hypertension: open-label pilot study. Chest. 2002 Jun;121(6):1860-8. [PubMed:12065350]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Stavros F, Kramer WG, Wilkins MR: The effects of sitaxentan on sildenafil pharmacokinetics and pharmacodynamics in healthy subjects. Br J Clin Pharmacol. 2010 Jan;69(1):23-6. doi: 10.1111/j.1365-2125.2009.03541.x. [PubMed:20078609]
  2. Barst RJ, Rich S, Widlitz A, Horn EM, McLaughlin V, McFarlin J: Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonist, in patients with pulmonary arterial hypertension: open-label pilot study. Chest. 2002 Jun;121(6):1860-8. [PubMed:12065350]

Drug created on March 19, 2008 10:20 / Updated on November 09, 2017 03:53