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Identification
NameBosentan
Accession NumberDB00559  (APRD00829)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Bosentan is a dual endothelin receptor antagonist important in the treatment of pulmonary artery hypertension (PAH). It is licensed in the United States, the European Union and other countries by Actelion Pharmaceuticals for the management of PAH under the trade name Tracleer®. Bosentan is used to treat pulmonary hypertension by blocking the action of endothelin molecules that would otherwise promote narrowing of the blood vessels and lead to high blood pressure.

Structure
Thumb
Synonyms
SynonymLanguageCode
4-(1,1-Dimethylethyl)-N-(6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-(2,2'-bipyrimidin)-4-yl) benzenesulfornamideNot AvailableNot Available
Bosentan hydrateNot AvailableNot Available
BosentanumNot AvailableNot Available
P-Tert-butyl-N-(6-(2-hydroxyethoxy)-5-(O-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl)benzenesulfonamideNot AvailableNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Tracleertablet, film coated62.5 mgoralActelion Pharmaceuticals US, Inc.2001-11-20Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tracleertablet, film coated125 mgoralActelion Pharmaceuticals US, Inc.2001-11-20Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tracleertablet62.5 mgoralActelion Pharmaceuticals LtdNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Tracleertablet125 mgoralActelion Pharmaceuticals LtdNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number147536-97-8
WeightAverage: 551.614
Monoisotopic: 551.183854375
Chemical FormulaC27H29N5O6S
InChI KeyGJPICJJJRGTNOD-UHFFFAOYSA-N
InChI
InChI=1S/C27H29N5O6S/c1-27(2,3)18-10-12-19(13-11-18)39(34,35)32-23-22(38-21-9-6-5-8-20(21)36-4)26(37-17-16-33)31-25(30-23)24-28-14-7-15-29-24/h5-15,33H,16-17H2,1-4H3,(H,30,31,32)
IUPAC Name
4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]benzene-1-sulfonamide
SMILES
COC1=CC=CC=C1OC1=C(NS(=O)(=O)C2=CC=C(C=C2)C(C)(C)C)N=C(N=C1OCCO)C1=NC=CC=N1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as bipyrimidines and oligopyrimidines. These are organic compounds containing two or more pyrimidine rings directly linked to each other. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazines
Sub ClassPyrimidines and pyrimidine derivatives
Direct ParentBipyrimidines and oligopyrimidines
Alternative Parents
Substituents
  • Bipyrimidine
  • Diaryl ether
  • Benzenesulfonamide
  • Phenylpropane
  • Methoxybenzene
  • Phenol ether
  • Anisole
  • Aminopyrimidine
  • Alkyl aryl ether
  • Imidolactam
  • Benzenoid
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Aminosulfonyl compound
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Azacycle
  • Ether
  • Hydrocarbon derivative
  • Primary alcohol
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Alcohol
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationUsed in the treatment of pulmonary arterial hypertension (PAH), to improve exercise ability and to decrease the rate of clinical worsening (in patients with WHO Class III or IV symptoms).
PharmacodynamicsBosentan 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. Bosentan blocks the binding of endothelin to its receptors, thereby negating endothelin's deleterious effects.
Mechanism of actionEndothelin-1 (ET-1) is a neurohormone, the effects of which are mediated by binding to ETA and ETB receptors in the endothelium and vascular smooth muscle. ET-1 concentrations are elevated in plasma and lung tissue of patients with pulmonary arterial hypertension, suggesting a pathogenic role for ET-1 in this disease. Bosentan is a specific and competitive antagonist at endothelin receptor types ETA and ETB. Bosentan has a slightly higher affinity for ETA receptors than for ETB receptors.
AbsorptionAbsolute bioavailability is approximately 50% and food does not affect absorption.
Volume of distribution
  • 18 L
Protein bindingGreater than 98% to plasma proteins, mainly albumin.
Metabolism

Bosentan is metabolized in the liver by the cytochrome P450 enzymes CYP2C9 and CYP3A4 (and possibly CYP2C19), producing three metabolites, one of which, Ro 48-5033, is pharmacologically active and may contribute 10 to 20% to the total activity of the parent compound.

SubstrateEnzymesProduct
Bosentan
Bosentan metabolite Ro 48-5033Details
Bosentan
Bosentan metabolite Ro 47-8634Details
Bosentan metabolite Ro 48-5033
Not Available
Bosentan metabolite Ro 64-1056Details
Bosentan metabolite Ro 47-8634
Not Available
Bosentan metabolite Ro 64-1056Details
Route of eliminationBosentan is eliminated by biliary excretion following metabolism in the liver.
Half lifeTerminal elimination half-life is about 5 hours in healthy adult subjects.
Clearance
  • 4 L/h [patients with pulmonary arterial hypertension]
ToxicityBosentan has been given as a single dose of up to 2400 mg in normal volunteers, or up to 2000 mg/day for 2 months in patients, without any major clinical consequences. The most common side effect was headache of mild to moderate intensity. In the cyclosporine A interaction study, in which doses of 500 and 1000 mg b.i.d. of bosentan were given concomitantly with cyclosporine A, trough plasma concentrations of bosentan increased 30-fold, resulting in severe headache, nausea, and vomiting, but no serious adverse events. Mild decreases in blood pressure and increases in heart rate were observed. There is no specific experience of overdosage with bosentan beyond the doses described above. Massive overdosage may result in pronounced hypotension requiring active cardiovascular support.
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+0.9253
Blood Brain Barrier-0.7419
Caco-2 permeable-0.8956
P-glycoprotein substrateNon-substrate0.5738
P-glycoprotein inhibitor INon-inhibitor0.6175
P-glycoprotein inhibitor IINon-inhibitor0.5092
Renal organic cation transporterNon-inhibitor0.9149
CYP450 2C9 substrateNon-substrate0.5926
CYP450 2D6 substrateNon-substrate0.9117
CYP450 3A4 substrateSubstrate0.5132
CYP450 1A2 substrateNon-inhibitor0.7203
CYP450 2C9 substrateInhibitor0.518
CYP450 2D6 substrateNon-inhibitor0.8755
CYP450 2C19 substrateNon-inhibitor0.5219
CYP450 3A4 substrateInhibitor0.8407
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.772
Ames testNon AMES toxic0.6147
CarcinogenicityNon-carcinogens0.6515
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.2676 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9679
hERG inhibition (predictor II)Non-inhibitor0.572
Pharmacoeconomics
Manufacturers
  • Actelion ltd
Packagers
Dosage forms
FormRouteStrength
Tabletoral125 mg
Tabletoral62.5 mg
Tablet, film coatedoral125 mg
Tablet, film coatedoral62.5 mg
PricesNot Available
Patents
CountryPatent NumberApprovedExpires (estimated)
Canada20711931998-08-252012-06-12
United States52927401995-11-202015-11-20
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilityPoorly soluble in water (1.0 mg/100 ml) and in aqueous solutions at low pH (0.1 mg/100 ml at pH 1.1 and 4.0; 0.2 mg/100 ml at pH 5.0). Solubility increases at higher pH values (43 mg/100 ml at pH 7.5).Not Available
logP3.7Not Available
Caco2 permeability-5.98ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.00904 mg/mLALOGPS
logP4.18ALOGPS
logP4.94ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)5.8ChemAxon
pKa (Strongest Basic)-0.43ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area145.65 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity166.66 m3·mol-1ChemAxon
Polarizability57.89 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Maurizio TADDEI, Diletta Naldini, Pietro Allegrini, Gabriele Razzetti, Simone Mantegazza, “Process for the Preparation of Bosentan.” U.S. Patent US20090156811, issued June 18, 2009.

US20090156811
General ReferenceNot Available
External Links
ATC CodesC02KX01
AHFS Codes
  • 24:12.92
PDB EntriesNot Available
FDA labelDownload (424 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AbirateroneMay decrease the serum concentration of CYP3A4 Substrates.
AcenocoumarolMay increase the metabolism of Vitamin K Antagonists.
AlfuzosinMay decrease the serum concentration of CYP3A4 Substrates.
AlprazolamMay decrease the serum concentration of CYP3A4 Substrates.
AminophyllineMay decrease the serum concentration of CYP3A4 Substrates.
AmiodaroneMay decrease the serum concentration of CYP3A4 Substrates.
AmlodipineMay decrease the serum concentration of CYP3A4 Substrates.
ApixabanMay decrease the serum concentration of CYP3A4 Substrates.
ApremilastMay decrease the serum concentration of CYP3A4 Substrates.
AprepitantMay decrease the serum concentration of CYP3A4 Substrates.
AripiprazoleCYP3A4 Inducers may decrease the serum concentration of ARIPiprazole.
armodafinilMay decrease the serum concentration of CYP3A4 Substrates.
ArtemetherMay decrease the serum concentration of CYP3A4 Substrates.
AtazanavirMay increase the serum concentration of Bosentan. Bosentan may decrease the serum concentration of Atazanavir.
AtorvastatinMay increase the metabolism of HMG-CoA Reductase Inhibitors.
AvanafilMay decrease the serum concentration of Phosphodiesterase 5 Inhibitors. Phosphodiesterase 5 Inhibitors may increase the serum concentration of Bosentan.
AxitinibCYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib.
BedaquilineMay decrease the serum concentration of CYP3A4 Substrates.
BenzphetamineMay decrease the serum concentration of CYP3A4 Substrates.
BicalutamideCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosentan.
BiotinMay decrease the serum concentration of CYP3A4 Substrates.
BisoprololMay decrease the serum concentration of CYP3A4 Substrates.
BoceprevirMay increase the serum concentration of Bosentan. Bosentan may decrease the serum concentration of Boceprevir.
BortezomibMay decrease the serum concentration of CYP3A4 Substrates.
BosutinibCYP3A4 Inducers (Moderate) may decrease the serum concentration of Bosutinib.
BuprenorphineMay decrease the serum concentration of CYP3A4 Substrates.
BuspironeMay decrease the serum concentration of CYP3A4 Substrates.
CabazitaxelMay decrease the serum concentration of CYP3A4 Substrates.
CabozantinibMay decrease the serum concentration of CYP3A4 Substrates.
CalcitriolMay decrease the serum concentration of CYP3A4 Substrates.
CapecitabineCYP2C9 Inhibitors (Strong) may increase the serum concentration of Bosentan.
CarbamazepineMay decrease the serum concentration of CYP3A4 Substrates.
ChlordiazepoxideMay decrease the serum concentration of CYP3A4 Substrates.
ChloroquineMay decrease the serum concentration of CYP3A4 Substrates.
CilostazolMay decrease the serum concentration of CYP3A4 Substrates.
CimetidineCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosentan.
CitalopramMay decrease the serum concentration of CYP3A4 Substrates.
ClarithromycinCYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Clarithromycin. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Clarithromycin.
ClidiniumMay decrease the serum concentration of CYP3A4 Substrates.
ClonazepamMay decrease the serum concentration of CYP3A4 Substrates.
ClotrimazoleCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosentan.
ConivaptanMay decrease the serum concentration of CYP3A4 Substrates.
CrizotinibMay decrease the serum concentration of CYP3A4 Substrates.
Cyproterone acetateMay decrease the serum concentration of CYP3A4 Substrates.
DantroleneMay decrease the serum concentration of CYP3A4 Substrates.
DarifenacinMay decrease the serum concentration of CYP3A4 Substrates.
DarunavirBosentan may decrease the serum concentration of Darunavir. Darunavir may increase the serum concentration of Bosentan.
DasatinibMay decrease the serum concentration of CYP3A4 Substrates.
DelavirdineMay decrease the serum concentration of CYP3A4 Substrates.
DesipramineCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosentan.
DesogestrelMay decrease the serum concentration of Contraceptives (Estrogens).
DiazepamMay decrease the serum concentration of CYP3A4 Substrates.
DiltiazemMay decrease the serum concentration of CYP3A4 Substrates.
DisopyramideMay decrease the serum concentration of CYP3A4 Substrates.
DocetaxelMay decrease the serum concentration of CYP3A4 Substrates.
DoxazosinMay decrease the serum concentration of CYP3A4 Substrates.
DronedaroneMay decrease the serum concentration of CYP3A4 Substrates.
DrospirenoneMay decrease the serum concentration of Contraceptives (Progestins).
EliglustatMay decrease the serum concentration of CYP3A4 Substrates.
EltrombopagMay increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
EnzalutamideCYP3A4 Inducers (Moderate) may decrease the serum concentration of Enzalutamide.
EplerenoneMay decrease the serum concentration of CYP3A4 Substrates.
ErlotinibMay decrease the serum concentration of CYP3A4 Substrates.
EscitalopramMay decrease the serum concentration of CYP3A4 Substrates.
EstropipateMay decrease the serum concentration of CYP3A4 Substrates.
EszopicloneMay decrease the serum concentration of CYP3A4 Substrates.
Ethinyl EstradiolMay decrease the serum concentration of Contraceptives (Estrogens).
EthosuximideMay decrease the serum concentration of CYP3A4 Substrates.
EthynodiolMay decrease the serum concentration of Contraceptives (Estrogens).
EtonogestrelMay decrease the serum concentration of Contraceptives (Progestins).
EtoposideMay decrease the serum concentration of CYP3A4 Substrates.
EtravirineMay decrease the serum concentration of CYP3A4 Substrates.
EverolimusMay decrease the serum concentration of CYP3A4 Substrates.
ExemestaneMay decrease the serum concentration of CYP3A4 Substrates.
FelbamateMay decrease the serum concentration of CYP3A4 Substrates.
FelodipineMay decrease the serum concentration of CYP3A4 Substrates.
FentanylCYP3A4 Inducers (Moderate) may decrease the serum concentration of FentaNYL.
FesoterodineMay decrease the serum concentration of CYP3A4 Substrates.
FloxuridineCYP2C9 Inhibitors (Strong) may increase the serum concentration of Bosentan.
FluconazoleCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosentan.
FlurazepamMay decrease the serum concentration of CYP3A4 Substrates.
FlutamideMay decrease the serum concentration of CYP3A4 Substrates.
FluvastatinCYP2C9 Inhibitors (Moderate) may increase the serum concentration of Bosentan.
FosamprenavirBosentan may decrease the serum concentration of Fosamprenavir. Fosamprenavir may increase the serum concentration of Bosentan.
FosaprepitantMay decrease the serum concentration of CYP3A4 Substrates.
GefitinibMay decrease the serum concentration of CYP3A4 Substrates.
GemfibrozilCYP2C9 Inhibitors (Strong) may increase the serum concentration of Bosentan.
GlyburideMay enhance the hepatotoxic effect of Bosentan. Bosentan may increase the metabolism of GlyBURIDE. GlyBURIDE may increase the metabolism of Bosentan.
GuanfacineMay decrease the serum concentration of CYP3A4 Substrates.
HaloperidolMay decrease the serum concentration of CYP3A4 Substrates.
HydrocodoneCYP3A4 Inducers (Moderate) may decrease the serum concentration of Hydrocodone.
IfosfamideCYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Ifosfamide.
IndinavirMay decrease the serum concentration of Indinavir. Indinavir may increase the serum concentration of Bosentan.
IrbesartanCYP2C9 Inhibitors (Moderate) may increase the serum concentration of Bosentan.
IrinotecanMay decrease the serum concentration of CYP3A4 Substrates.
IsavuconazoniumMay decrease the serum concentration of CYP3A4 Substrates.
Isosorbide DinitrateMay decrease the serum concentration of CYP3A4 Substrates.
Isosorbide MononitrateMay decrease the serum concentration of CYP3A4 Substrates.
IsradipineMay decrease the serum concentration of CYP3A4 Substrates.
ItraconazoleMay decrease the serum concentration of CYP3A4 Substrates.
IvacaftorMay decrease the serum concentration of CYP3A4 Substrates.
IxabepiloneMay decrease the serum concentration of CYP3A4 Substrates.
LansoprazoleMay decrease the serum concentration of CYP3A4 Substrates.
LapatinibMay decrease the serum concentration of CYP3A4 Substrates.
LeflunomideCYP2C9 Inhibitors (Moderate) may increase the serum concentration of Bosentan.
LevonorgestrelMay decrease the serum concentration of Contraceptives (Progestins).
LinagliptinMay decrease the serum concentration of CYP3A4 Substrates.
LomitapideMay decrease the serum concentration of CYP3A4 Substrates.
LopinavirBosentan may decrease the serum concentration of Lopinavir. Lopinavir may increase the serum concentration of Bosentan.
LosartanMay decrease the serum concentration of CYP3A4 Substrates.
LovastatinMay increase the metabolism of HMG-CoA Reductase Inhibitors.
LumefantrineMay decrease the serum concentration of CYP3A4 Substrates.
LurasidoneMay decrease the serum concentration of CYP3A4 Substrates.
MACITENTANMay decrease the serum concentration of CYP3A4 Substrates.
MaravirocMay decrease the serum concentration of CYP3A4 Substrates.
Medroxyprogesterone AcetateMay decrease the serum concentration of Contraceptives (Progestins).
MefloquineMay decrease the serum concentration of CYP3A4 Substrates.
MestranolMay decrease the serum concentration of Contraceptives (Estrogens).
MethadoneMay decrease the serum concentration of CYP3A4 Substrates.
MidazolamMay decrease the serum concentration of CYP3A4 Substrates.
MifepristoneMay decrease the serum concentration of CYP3A4 Substrates.
MirtazapineMay decrease the serum concentration of CYP3A4 Substrates.
ModafinilMay decrease the serum concentration of CYP3A4 Substrates.
NateglinideMay decrease the serum concentration of CYP3A4 Substrates.
NefazodoneMay decrease the serum concentration of CYP3A4 Substrates.
NelfinavirMay decrease the serum concentration of Nelfinavir. Nelfinavir may increase the serum concentration of Bosentan.
NevirapineMay decrease the serum concentration of CYP3A4 Substrates.
NifedipineMay decrease the serum concentration of CYP3A4 Substrates.
NilotinibMay decrease the serum concentration of CYP3A4 Substrates.
NimodipineMay decrease the serum concentration of CYP3A4 Substrates.
NisoldipineCYP3A4 Inducers (Moderate) may decrease the serum concentration of Nisoldipine.
NorelgestrominMay decrease the serum concentration of Contraceptives (Estrogens).
NorethindroneMay decrease the serum concentration of Contraceptives (Progestins).
NorfloxacinCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosentan.
NorgestimateMay decrease the serum concentration of Contraceptives (Progestins).
OmeprazoleCYP2C9 Inhibitors (Moderate) may increase the serum concentration of Bosentan.
OndansetronMay decrease the serum concentration of CYP3A4 Substrates.
OspemifeneMay decrease the serum concentration of CYP3A4 Substrates.
OxycodoneMay decrease the serum concentration of CYP3A4 Substrates.
PanobinostatMay decrease the serum concentration of CYP3A4 Substrates.
PazopanibMay decrease the serum concentration of CYP3A4 Substrates.
PerampanelMay decrease the serum concentration of CYP3A4 Substrates.
PimozideMay decrease the serum concentration of CYP3A4 Substrates.
PiperazineMay decrease the serum concentration of CYP3A4 Substrates.
PipotiazineMay decrease the serum concentration of CYP3A4 Substrates.
PitavastatinMay increase the metabolism of HMG-CoA Reductase Inhibitors.
PomalidomideMay decrease the serum concentration of CYP3A4 Substrates.
PosaconazoleCYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosentan.
PraziquantelMay decrease the serum concentration of CYP3A4 Substrates.
PrimaquineMay decrease the serum concentration of CYP3A4 Substrates.
ProgesteroneMay decrease the serum concentration of CYP3A4 Substrates.
PyrimethamineCYP2C9 Inhibitors (Moderate) may increase the serum concentration of Bosentan.
QuetiapineMay decrease the serum concentration of CYP3A4 Substrates.
QuinidineMay decrease the serum concentration of CYP3A4 Substrates.
QuinineMay decrease the serum concentration of CYP3A4 Substrates.
RabeprazoleMay decrease the serum concentration of CYP3A4 Substrates.
RanolazineMay decrease the serum concentration of CYP3A4 Substrates.
RegorafenibMay decrease the serum concentration of CYP3A4 Substrates.
RepaglinideMay decrease the serum concentration of CYP3A4 Substrates.
RifampicinRifampin may decrease the serum concentration of Bosentan. Following the initial several weeks of concurrent rifampin, this effect is most likely. Rifampin may increase the serum concentration of Bosentan. This effect is most likely to be observed within the initial few weeks of concurrent therapy (and may be greatest immediately following initiation of the combination).
RilpivirineMay decrease the serum concentration of CYP3A4 Substrates.
RiociguatMay decrease the serum concentration of CYP3A4 Substrates.
RitonavirRitonavir may increase the serum concentration of Bosentan.
RivaroxabanMay decrease the serum concentration of CYP3A4 Substrates.
RoflumilastMay decrease the serum concentration of CYP3A4 Substrates.
RuxolitinibMay decrease the serum concentration of CYP3A4 Substrates.
SaquinavirBosentan may decrease the serum concentration of Saquinavir. Saquinavir may increase the serum concentration of Bosentan.
SaxagliptinCYP3A4 Inducers may decrease the serum concentration of Saxagliptin.
SildenafilMay decrease the serum concentration of Phosphodiesterase 5 Inhibitors. Phosphodiesterase 5 Inhibitors may increase the serum concentration of Bosentan.
SilodosinMay decrease the serum concentration of CYP3A4 Substrates.
SimeprevirCYP3A4 Inducers (Moderate) may decrease the serum concentration of Simeprevir.
SimvastatinMay increase the metabolism of HMG-CoA Reductase Inhibitors.
SirolimusMay decrease the serum concentration of CYP3A4 Substrates.
SolifenacinMay decrease the serum concentration of CYP3A4 Substrates.
SorafenibCYP2C9 Inhibitors (Moderate) may increase the serum concentration of Bosentan.
SpiramycinMay decrease the serum concentration of CYP3A4 Substrates.
SulfadiazineCYP2C9 Inhibitors (Strong) may increase the serum concentration of Bosentan.
SulfamethoxazoleMay decrease the serum concentration of CYP3A4 Substrates.
SulfisoxazoleMay decrease the serum concentration of CYP3A4 Substrates.
SunitinibMay decrease the serum concentration of CYP3A4 Substrates.
SuvorexantMay decrease the serum concentration of CYP3A4 Substrates.
TadalafilBosentan may decrease the serum concentration of Phosphodiesterase 5 Inhibitors. Phosphodiesterase 5 Inhibitors may increase the serum concentration of Bosentan.
TamoxifenMay decrease the serum concentration of CYP3A4 Substrates.
TamsulosinMay decrease the serum concentration of CYP3A4 Substrates.
TelaprevirBosentan may decrease the serum concentration of Telaprevir. Telaprevir may increase the serum concentration of Bosentan.
TelithromycinMay decrease the serum concentration of CYP3A4 Substrates.
TemsirolimusMay decrease the serum concentration of CYP3A4 Substrates.
TeniposideMay decrease the serum concentration of CYP3A4 Substrates.
TeriflunomideMay increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
TetracyclineMay decrease the serum concentration of CYP3A4 Substrates.
TheophyllineMay decrease the serum concentration of CYP3A4 Substrates.
TiagabineMay decrease the serum concentration of CYP3A4 Substrates.
TicagrelorMay decrease the serum concentration of CYP3A4 Substrates.
TiclopidineMay decrease the serum concentration of CYP3A4 Substrates.
TipranavirBosentan may decrease the serum concentration of Tipranavir. Tipranavir may increase the serum concentration of Bosentan.
TofacitinibMay decrease the serum concentration of CYP3A4 Substrates.
TolbutamideCYP2C9 Inhibitors (Strong) may increase the serum concentration of Bosentan.
TolterodineMay decrease the serum concentration of CYP3A4 Substrates.
TolvaptanMay decrease the serum concentration of CYP3A4 Substrates.
ToremifeneMay decrease the serum concentration of CYP3A4 Substrates.
TrabectedinMay decrease the serum concentration of CYP3A4 Substrates.
TramadolMay decrease the serum concentration of CYP3A4 Substrates.
TriazolamMay decrease the serum concentration of CYP3A4 Substrates.
TrimethoprimMay decrease the serum concentration of CYP3A4 Substrates.
TrimipramineMay decrease the serum concentration of CYP3A4 Substrates.
UlipristalBosentan may decrease the serum concentration of Ulipristal.
VandetanibMay decrease the serum concentration of CYP3A4 Substrates.
VardenafilBosentan may decrease the serum concentration of Phosphodiesterase 5 Inhibitors. Phosphodiesterase 5 Inhibitors may increase the serum concentration of Bosentan.
VemurafenibMay decrease the serum concentration of CYP3A4 Substrates.
VenlafaxineMay decrease the serum concentration of CYP3A4 Substrates.
VilazodoneMay decrease the serum concentration of CYP3A4 Substrates.
VinblastineMay decrease the serum concentration of CYP3A4 Substrates.
VincristineMay decrease the serum concentration of CYP3A4 Substrates.
VinorelbineMay decrease the serum concentration of CYP3A4 Substrates.
VoriconazoleCYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosentan.
ZafirlukastCYP2C9 Inhibitors (Moderate) may increase the serum concentration of Bosentan.
ZolpidemMay decrease the serum concentration of CYP3A4 Substrates.
ZonisamideMay decrease the serum concentration of CYP3A4 Substrates.
ZopicloneMay decrease the serum concentration of CYP3A4 Substrates.
Food Interactions
  • Take without regard to meals.

Targets

1. Endothelin B receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Endothelin B receptor P24530 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. 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
  3. 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
  4. Marano G, Palazzesi S, Bernucci P, Grigioni M, Formigari R, Ballerini L: ET/ET receptor antagonist bosentan inhibits neointimal development in collared carotid arteries of rabbits. Life Sci. 1998;63(18):PL259-66. Pubmed
  5. 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
  6. 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

2. Endothelin-1 receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Endothelin-1 receptor P25101 Details

References:

  1. 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
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  3. 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
  4. 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
  5. Martin C, Held HD, Uhlig S: Differential effects of the mixed ET/ET-receptor antagonist bosentan on endothelin-induced bronchoconstriction, vasoconstriction and prostacyclin release. Naunyn Schmiedebergs Arch Pharmacol. 2000 Aug;362(2):128-36. Pubmed
  6. 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

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inducer

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Dingemanse J, Schaarschmidt D, van Giersbergen PL: Investigation of the mutual pharmacokinetic interactions between bosentan, a dual endothelin receptor antagonist, and simvastatin. Clin Pharmacokinet. 2003;42(3):293-301. Pubmed
  2. Dingemanse J, van Giersbergen PL: Clinical pharmacology of bosentan, a dual endothelin receptor antagonist. Clin Pharmacokinet. 2004;43(15):1089-115. Pubmed
  3. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inducer

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Transporters

1. Bile salt export pump

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Bile salt export pump O95342 Details

References:

  1. Fattinger K, Funk C, Pantze M, Weber C, Reichen J, Stieger B, Meier PJ: The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: a potential mechanism for hepatic adverse reactions. Clin Pharmacol Ther. 2001 Apr;69(4):223-31. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11