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Identification
NameSitaxentan
Accession NumberDB06268
TypeSmall Molecule
GroupsApproved, Investigational, Withdrawn
DescriptionSitaxentan 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 Identifiers
  • IPI-1040
  • TBC-11251
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Thelintablet100 mgoralPfizer Canada Inc2007-06-192011-04-30Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ThelinFilm-coated tablet100 mgOral usePfizer Ltd.2006-08-10Not applicableEu
ThelinFilm-coated tablet100 mgOral usePfizer Ltd.2006-08-10Not applicableEu
ThelinFilm-coated tablet100 mgOral usePfizer Ltd.2006-08-10Not applicableEu
ThelinFilm-coated tablet100 mgOral usePfizer Ltd.2006-08-10Not applicableEu
ThelinFilm-coated tablet100 mgOral usePfizer Ltd.2006-08-10Not applicableEu
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Sitaxentan sodium
210421-74-2
Thumb
  • InChI Key: MDTNUYUCUYPIHE-UHFFFAOYSA-N
  • Monoisotopic Mass: 475.9879505
  • Average Mass: 476.88
DBSALT001120
Categories
UNIIJ9QH779MEM
CAS number184036-34-8
WeightAverage: 454.905
Monoisotopic: 454.006005309
Chemical FormulaC18H15ClN2O6S2
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzodioxoles
Sub ClassNot Available
Direct ParentBenzodioxoles
Alternative Parents
Substituents
  • Benzodioxole
  • Aryl alkyl ketone
  • Aryl ketone
  • Benzenoid
  • Aryl halide
  • Aryl chloride
  • Heteroaromatic compound
  • Aminosulfonyl compound
  • Thiophene
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Oxazole
  • Isoxazole
  • Azole
  • Ketone
  • Oxacycle
  • Azacycle
  • Acetal
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationInvestigated for use/treatment in pulmonary hypertension, connective tissue diseases, hypertension, and congestive heart failure.
PharmacodynamicsSitaxentan 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 actionSitaxentan 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.
Related Articles
Absorption70-100%
Volume of distributionNot Available
Protein binding99% +
Metabolism

Hepatic (CYP2C9- and CYP3A4-mediated)

Route of eliminationRenal (50 to 60%) Fecal (40 to 50%)
Half life10 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Film-coated tabletOral use100 mg
Tabletoral100 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2161346 No2004-11-232014-05-20Canada
CA2281090 No2005-06-072018-04-02Canada
Properties
StateSolid
Experimental PropertiesNot 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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesC02KX03
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
7,8-DICHLORO-1,2,3,4-TETRAHYDROISOQUINOLINE7,8-DICHLORO-1,2,3,4-TETRAHYDROISOQUINOLINE may increase the hypotensive activities of Sitaxentan.
AbirateroneThe metabolism of Sitaxentan can be decreased when combined with Abiraterone.
AcebutololAcebutolol may increase the hypotensive activities of Sitaxentan.
AlfuzosinAlfuzosin may increase the hypotensive activities of Sitaxentan.
AliskirenAliskiren may increase the hypotensive activities of Sitaxentan.
AlprenololAlprenolol may increase the hypotensive activities of Sitaxentan.
AmbrisentanSitaxentan may increase the hypotensive activities of Ambrisentan.
AmifostineSitaxentan may increase the hypotensive activities of Amifostine.
AmiodaroneThe metabolism of Sitaxentan can be decreased when combined with Amiodarone.
AmlodipineAmlodipine may increase the hypotensive activities of Sitaxentan.
AprepitantThe metabolism of Sitaxentan can be increased when combined with Aprepitant.
AtenololAtenolol may increase the hypotensive activities of Sitaxentan.
BenazeprilBenazepril may increase the hypotensive activities of Sitaxentan.
BendroflumethiazideBendroflumethiazide may increase the hypotensive activities of Sitaxentan.
BenmoxinBenmoxin may increase the hypotensive activities of Sitaxentan.
BepridilBepridil may increase the hypotensive activities of Sitaxentan.
BetaxololBetaxolol may increase the hypotensive activities of Sitaxentan.
BethanidineBethanidine may increase the hypotensive activities of Sitaxentan.
BimatoprostBimatoprost may increase the hypotensive activities of Sitaxentan.
BisoprololBisoprolol may increase the hypotensive activities of Sitaxentan.
BosentanBosentan may increase the hypotensive activities of Sitaxentan.
BretyliumBretylium may increase the hypotensive activities of Sitaxentan.
BrimonidineSitaxentan may increase the hypotensive activities of Brimonidine.
BrimonidineBrimonidine may increase the antihypertensive activities of Sitaxentan.
BupranololBupranolol may increase the hypotensive activities of Sitaxentan.
CandesartanCandesartan may increase the hypotensive activities of Sitaxentan.
CandoxatrilCandoxatril may increase the hypotensive activities of Sitaxentan.
CapecitabineThe metabolism of Sitaxentan can be decreased when combined with Capecitabine.
CaptoprilCaptopril may increase the hypotensive activities of Sitaxentan.
CarbamazepineThe metabolism of Sitaxentan can be increased when combined with Carbamazepine.
CaroxazoneCaroxazone may increase the hypotensive activities of Sitaxentan.
CarteololCarteolol may increase the hypotensive activities of Sitaxentan.
CarvedilolCarvedilol may increase the hypotensive activities of Sitaxentan.
CeliprololCeliprolol may increase the hypotensive activities of Sitaxentan.
CeritinibThe serum concentration of Sitaxentan can be increased when it is combined with Ceritinib.
ChlorothiazideChlorothiazide may increase the hypotensive activities of Sitaxentan.
ChlorthalidoneChlorthalidone may increase the hypotensive activities of Sitaxentan.
CholecalciferolThe metabolism of Sitaxentan can be decreased when combined with Cholecalciferol.
CilazaprilCilazapril may increase the hypotensive activities of Sitaxentan.
CilostazolThe serum concentration of Cilostazol can be increased when it is combined with Sitaxentan.
ClonidineClonidine may increase the hypotensive activities of Sitaxentan.
ClotrimazoleThe metabolism of Sitaxentan can be decreased when combined with Clotrimazole.
CryptenamineCryptenamine may increase the hypotensive activities of Sitaxentan.
CyclosporineThe serum concentration of Sitaxentan can be increased when it is combined with Cyclosporine.
CyclothiazideCyclothiazide may increase the hypotensive activities of Sitaxentan.
DabrafenibThe serum concentration of Sitaxentan can be decreased when it is combined with Dabrafenib.
DebrisoquinDebrisoquin may increase the hypotensive activities of Sitaxentan.
DelavirdineThe metabolism of Sitaxentan can be decreased when combined with Delavirdine.
DeserpidineDeserpidine may increase the hypotensive activities of Sitaxentan.
DiazoxideDiazoxide may increase the hypotensive activities of Sitaxentan.
DiltiazemDiltiazem may increase the hypotensive activities of Sitaxentan.
DorzolamideDorzolamide may increase the hypotensive activities of Sitaxentan.
DoxazosinDoxazosin may increase the hypotensive activities of Sitaxentan.
EfavirenzThe metabolism of Sitaxentan can be decreased when combined with Efavirenz.
EfonidipineEfonidipine may increase the hypotensive activities of Sitaxentan.
EnalaprilEnalapril may increase the hypotensive activities of Sitaxentan.
EnalaprilatEnalaprilat may increase the hypotensive activities of Sitaxentan.
EpoprostenolEpoprostenol may increase the hypotensive activities of Sitaxentan.
EprosartanEprosartan may increase the hypotensive activities of Sitaxentan.
EtravirineThe metabolism of Sitaxentan can be decreased when combined with Etravirine.
FelodipineFelodipine may increase the hypotensive activities of Sitaxentan.
FenoldopamFenoldopam may increase the hypotensive activities of Sitaxentan.
FloxuridineThe metabolism of Sitaxentan can be decreased when combined with Floxuridine.
FluconazoleThe metabolism of Sitaxentan can be decreased when combined with Fluconazole.
FluorouracilThe metabolism of Sitaxentan can be decreased when combined with Fluorouracil.
FluvastatinThe metabolism of Sitaxentan can be decreased when combined with Fluvastatin.
FluvoxamineThe metabolism of Sitaxentan can be decreased when combined with Fluvoxamine.
FosinoprilFosinopril may increase the hypotensive activities of Sitaxentan.
FosphenytoinThe metabolism of Sitaxentan can be increased when combined with Fosphenytoin.
FurazolidoneFurazolidone may increase the hypotensive activities of Sitaxentan.
GemfibrozilThe metabolism of Sitaxentan can be decreased when combined with Gemfibrozil.
GuanabenzGuanabenz may increase the hypotensive activities of Sitaxentan.
GuanadrelGuanadrel may increase the hypotensive activities of Sitaxentan.
GuanethidineGuanethidine may increase the hypotensive activities of Sitaxentan.
GuanfacineGuanfacine may increase the hypotensive activities of Sitaxentan.
HexamethoniumHexamethonium may increase the hypotensive activities of Sitaxentan.
HydracarbazineHydracarbazine may increase the hypotensive activities of Sitaxentan.
HydralazineHydralazine may increase the hypotensive activities of Sitaxentan.
HydrochlorothiazideHydrochlorothiazide may increase the hypotensive activities of Sitaxentan.
HydroflumethiazideHydroflumethiazide may increase the hypotensive activities of Sitaxentan.
IloprostIloprost may increase the hypotensive activities of Sitaxentan.
IndapamideIndapamide may increase the hypotensive activities of Sitaxentan.
IndenololIndenolol may increase the hypotensive activities of Sitaxentan.
IndinavirThe metabolism of Sitaxentan can be decreased when combined with Indinavir.
IndoraminIndoramin may increase the hypotensive activities of Sitaxentan.
IproclozideIproclozide may increase the hypotensive activities of Sitaxentan.
IproniazidIproniazid may increase the hypotensive activities of Sitaxentan.
IrbesartanIrbesartan may increase the hypotensive activities of Sitaxentan.
IsocarboxazidIsocarboxazid may increase the hypotensive activities of Sitaxentan.
IsradipineIsradipine may increase the hypotensive activities of Sitaxentan.
KetoconazoleThe metabolism of Sitaxentan can be decreased when combined with Ketoconazole.
LabetalolLabetalol may increase the hypotensive activities of Sitaxentan.
LacidipineLacidipine may increase the hypotensive activities of Sitaxentan.
LatanoprostLatanoprost may increase the hypotensive activities of Sitaxentan.
LeflunomideThe metabolism of Sitaxentan can be decreased when combined with Leflunomide.
LercanidipineLercanidipine may increase the hypotensive activities of Sitaxentan.
LisinoprilLisinopril may increase the hypotensive activities of Sitaxentan.
LofexidineLofexidine may increase the hypotensive activities of Sitaxentan.
LosartanLosartan may increase the hypotensive activities of Sitaxentan.
LovastatinThe metabolism of Sitaxentan can be decreased when combined with Lovastatin.
LumacaftorThe serum concentration of Sitaxentan can be decreased when it is combined with Lumacaftor.
MacitentanSitaxentan may increase the hypotensive activities of Macitentan.
ManidipineManidipine may increase the hypotensive activities of Sitaxentan.
MebanazineMebanazine may increase the hypotensive activities of Sitaxentan.
MecamylamineMecamylamine may increase the hypotensive activities of Sitaxentan.
MethyldopaMethyldopa may increase the hypotensive activities of Sitaxentan.
Methylene blueMethylene blue may increase the hypotensive activities of Sitaxentan.
MethylphenidateMethylphenidate may decrease the antihypertensive activities of Sitaxentan.
MetipranololMetipranolol may increase the hypotensive activities of Sitaxentan.
MetolazoneMetolazone may increase the hypotensive activities of Sitaxentan.
MetoprololMetoprolol may increase the hypotensive activities of Sitaxentan.
MibefradilMibefradil may increase the hypotensive activities of Sitaxentan.
MifepristoneThe serum concentration of Sitaxentan can be increased when it is combined with Mifepristone.
MinaprineMinaprine may increase the hypotensive activities of Sitaxentan.
MinoxidilMinoxidil may increase the hypotensive activities of Sitaxentan.
MoclobemideMoclobemide may increase the hypotensive activities of Sitaxentan.
MoexiprilMoexipril may increase the hypotensive activities of Sitaxentan.
MolsidomineMolsidomine may increase the hypotensive activities of Sitaxentan.
MoxonidineMoxonidine may increase the hypotensive activities of Sitaxentan.
NadololNadolol may increase the hypotensive activities of Sitaxentan.
NebivololNebivolol may increase the hypotensive activities of Sitaxentan.
NialamideNialamide may increase the hypotensive activities of Sitaxentan.
NicardipineNicardipine may increase the hypotensive activities of Sitaxentan.
NicorandilNicorandil may increase the hypotensive activities of Sitaxentan.
NiguldipineNiguldipine may increase the hypotensive activities of Sitaxentan.
NilvadipineNilvadipine may increase the hypotensive activities of Sitaxentan.
NimodipineNimodipine may increase the hypotensive activities of Sitaxentan.
NintedanibThe serum concentration of Nintedanib can be increased when it is combined with Sitaxentan.
NisoldipineNisoldipine may increase the hypotensive activities of Sitaxentan.
NitrendipineNitrendipine may increase the hypotensive activities of Sitaxentan.
NitroprussideNitroprusside may increase the hypotensive activities of Sitaxentan.
ObinutuzumabSitaxentan may increase the hypotensive activities of Obinutuzumab.
OctamoxinOctamoxin may increase the hypotensive activities of Sitaxentan.
OlmesartanOlmesartan may increase the hypotensive activities of Sitaxentan.
OmapatrilatOmapatrilat may increase the hypotensive activities of Sitaxentan.
OmeprazoleThe metabolism of Sitaxentan can be decreased when combined with Omeprazole.
OxprenololOxprenolol may increase the hypotensive activities of Sitaxentan.
PargylinePargyline may increase the hypotensive activities of Sitaxentan.
PenbutololPenbutolol may increase the hypotensive activities of Sitaxentan.
PentoliniumPentolinium may increase the hypotensive activities of Sitaxentan.
PentoxifyllinePentoxifylline may increase the hypotensive activities of Sitaxentan.
PerindoprilPerindopril may increase the hypotensive activities of Sitaxentan.
PhenelzinePhenelzine may increase the hypotensive activities of Sitaxentan.
PheniprazinePheniprazine may increase the hypotensive activities of Sitaxentan.
PhenobarbitalThe metabolism of Sitaxentan can be increased when combined with Phenobarbital.
PhenoxybenzaminePhenoxybenzamine may increase the hypotensive activities of Sitaxentan.
PhenoxypropazinePhenoxypropazine may increase the hypotensive activities of Sitaxentan.
PhentolaminePhentolamine may increase the hypotensive activities of Sitaxentan.
PhenytoinThe metabolism of Sitaxentan can be increased when combined with Phenytoin.
PinacidilPinacidil may increase the hypotensive activities of Sitaxentan.
PindololPindolol may increase the hypotensive activities of Sitaxentan.
PirlindolePirlindole may increase the hypotensive activities of Sitaxentan.
PivhydrazinePivhydrazine may increase the hypotensive activities of Sitaxentan.
PolythiazidePolythiazide may increase the hypotensive activities of Sitaxentan.
PrazosinPrazosin may increase the hypotensive activities of Sitaxentan.
PrimidoneThe metabolism of Sitaxentan can be increased when combined with Primidone.
PropranololPropranolol may increase the hypotensive activities of Sitaxentan.
PyrimethamineThe metabolism of Sitaxentan can be decreased when combined with Pyrimethamine.
QuinaprilQuinapril may increase the hypotensive activities of Sitaxentan.
QuinineQuinine may increase the hypotensive activities of Sitaxentan.
RamiprilRamipril may increase the hypotensive activities of Sitaxentan.
RasagilineRasagiline may increase the hypotensive activities of Sitaxentan.
RemikirenRemikiren may increase the hypotensive activities of Sitaxentan.
RescinnamineRescinnamine may increase the hypotensive activities of Sitaxentan.
ReserpineReserpine may increase the hypotensive activities of Sitaxentan.
RifampicinThe metabolism of Sitaxentan can be increased when combined with Rifampicin.
RifapentineThe metabolism of Sitaxentan can be increased when combined with Rifapentine.
RiociguatSitaxentan may increase the hypotensive activities of Riociguat.
RituximabSitaxentan may increase the hypotensive activities of Rituximab.
SafrazineSafrazine may increase the hypotensive activities of Sitaxentan.
SaprisartanSaprisartan may increase the hypotensive activities of Sitaxentan.
SecobarbitalThe metabolism of Sitaxentan can be increased when combined with Secobarbital.
SelegilineSelegiline may increase the hypotensive activities of Sitaxentan.
SelexipagSelexipag may increase the hypotensive activities of Sitaxentan.
SildenafilSildenafil may increase the antihypertensive activities of Sitaxentan.
SorafenibThe metabolism of Sitaxentan can be decreased when combined with Sorafenib.
SpiraprilSpirapril may increase the hypotensive activities of Sitaxentan.
SulfadiazineThe metabolism of Sitaxentan can be decreased when combined with Sulfadiazine.
SulfamethoxazoleThe metabolism of Sitaxentan can be decreased when combined with Sulfamethoxazole.
SulfisoxazoleThe metabolism of Sitaxentan can be decreased when combined with Sulfisoxazole.
TadalafilTadalafil may increase the antihypertensive activities of Sitaxentan.
TelmisartanTelmisartan may increase the hypotensive activities of Sitaxentan.
TemocaprilTemocapril may increase the hypotensive activities of Sitaxentan.
TerlipressinTerlipressin may increase the hypotensive activities of Sitaxentan.
TiboloneTibolone may increase the hypotensive activities of Sitaxentan.
TicagrelorThe metabolism of Sitaxentan can be decreased when combined with Ticagrelor.
TiclopidineThe metabolism of Sitaxentan can be decreased when combined with Ticlopidine.
TicrynafenTicrynafen may increase the hypotensive activities of Sitaxentan.
TimololTimolol may increase the hypotensive activities of Sitaxentan.
TofacitinibThe serum concentration of Tofacitinib can be increased when it is combined with Sitaxentan.
TolazolineTolazoline may increase the hypotensive activities of Sitaxentan.
TolbutamideThe metabolism of Sitaxentan can be decreased when combined with Tolbutamide.
ToloxatoneToloxatone may increase the hypotensive activities of Sitaxentan.
TorasemideTorasemide may increase the hypotensive activities of Sitaxentan.
TrandolaprilTrandolapril may increase the hypotensive activities of Sitaxentan.
Trans-2-PhenylcyclopropylamineTrans-2-Phenylcyclopropylamine may increase the hypotensive activities of Sitaxentan.
TranylcypromineTranylcypromine may increase the hypotensive activities of Sitaxentan.
TravoprostTravoprost may increase the hypotensive activities of Sitaxentan.
TreprostinilTreprostinil may increase the hypotensive activities of Sitaxentan.
TrichlormethiazideTrichlormethiazide may increase the hypotensive activities of Sitaxentan.
TrimazosinTrimazosin may increase the hypotensive activities of Sitaxentan.
TrimethaphanTrimethaphan may increase the hypotensive activities of Sitaxentan.
TrimethoprimThe metabolism of Sitaxentan can be decreased when combined with Trimethoprim.
UdenafilUdenafil may increase the antihypertensive activities of Sitaxentan.
UnoprostoneUnoprostone may increase the hypotensive activities of Sitaxentan.
Valproic AcidThe metabolism of Sitaxentan can be decreased when combined with Valproic Acid.
ValsartanValsartan may increase the hypotensive activities of Sitaxentan.
VardenafilVardenafil may increase the antihypertensive activities of Sitaxentan.
VoriconazoleThe metabolism of Sitaxentan can be decreased when combined with Voriconazole.
WarfarinThe serum concentration of Warfarin can be increased when it is combined with Sitaxentan.
XylometazolineXylometazoline may increase the hypotensive activities of Sitaxentan.
YohimbineYohimbine may decrease the antihypertensive activities of Sitaxentan.
ZafirlukastThe metabolism of Sitaxentan can be decreased when combined with Zafirlukast.
Food Interactions
  • Take without regard to meals

Targets

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: ET1 > ET2 >> ET3.
Gene Name:
EDNRA
Uniprot ID:
P25101
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 ]
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
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 imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
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
substrateinhibitor
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
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 ]
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Drug created on March 19, 2008 10:20 / Updated on August 17, 2016 12:24