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Identification
NameTirofiban
Accession NumberDB00775  (APRD00304)
Typesmall molecule
Groupsapproved
Description

Tirofiban prevents the blood from clotting during episodes of chest pain or a heart attack, or while the patient is undergoing a procedure to treat a blocked coronary artery. It is a non-peptide reversible antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor, and inhibits platelet aggregation.

Structure
Thumb
Synonyms
SynonymLanguageCode
TirofibanNot AvailableINN, BAN
SaltsNot Available
Brand names
NameCompany
AggrastatMedicure Pharma
AggriblocAbbott
AgrastatMerck Sharp & Dohme
Brand mixturesNot Available
Categories
CAS number144494-65-5
WeightAverage: 440.597
Monoisotopic: 440.234492962
Chemical FormulaC22H36N2O5S
InChI KeyCOKMIXFXJJXBQG-NRFANRHFSA-N
InChI
InChI=1S/C22H36N2O5S/c1-2-3-16-30(27,28)24-21(22(25)26)17-19-7-9-20(10-8-19)29-15-5-4-6-18-11-13-23-14-12-18/h7-10,18,21,23-24H,2-6,11-17H2,1H3,(H,25,26)/t21-/m0/s1
IUPAC Name
(2S)-2-(butane-1-sulfonamido)-3-{4-[4-(piperidin-4-yl)butoxy]phenyl}propanoic acid
SMILES
CCCCS(=O)(=O)N[C@@H](CC1=CC=C(OCCCCC2CCNCC2)C=C1)C(O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassPhenylpropanoids and Polyketides
ClassPhenylpropanoic Acids
SubclassNot Available
Direct parentPhenylpropanoic Acids
Alternative parentsAmphetamines and Derivatives; Alpha Amino Acids and Derivatives; Phenol Ethers; Amino Fatty Acids; Alkyl Aryl Ethers; Piperidines; Sulfonyls; Sulfonamides; Polyamines; Dialkylamines; Carboxylic Acids; Enolates
Substituentsphenol ether; alkyl aryl ether; benzene; piperidine; sulfonyl; sulfonic acid derivative; sulfonamide; secondary amine; carboxylic acid derivative; secondary aliphatic amine; carboxylic acid; enolate; ether; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the phenylpropanoic acids. These are compounds whose structure contain a benzene ring conjugated to a propanoic acid.
Pharmacology
IndicationFor treatment, in combination with heparin, of acute coronary syndrome, including patients who are to be managed medically and those undergoing PTCA or atherectomy.
PharmacodynamicsTirofiban prevents the blood from clotting during episodes of chest pain or a heart attack, or while the patient is undergoing a procedure to treat a blocked coronary artery. It is a non-peptide antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor, and inhibits platelet aggregation. When administered intravenously, tirofiban inhibits ex vivo platelet aggregation in a dose- and concentration-dependent manner. When given according to the recommended regimen, >90% inhibition is attained by the end of the 30-minute infusion. Tirofiban has been recently shown in patients with unstable angina to reduce ischemic events at 48 hours following infusion when compared to standard heparin therapy.
Mechanism of actionTirofiban is a reversible antagonist of fibrinogen binding to the GP IIb/IIIa receptor, the major platelet surface receptor involved in platelet aggregation. Platelet aggregation inhibition is reversible following cessation of the infusion of tirofiban.
AbsorptionNot Available
Volume of distribution
  • 22 to 42 L
Protein binding65%
Metabolism

Metabolism appears to be limited.

Route of eliminationIt is cleared from the plasma largely by renal excretion, with about 65% of an administered dose appearing in urine and about 25% in feces, both largely as unchanged tirofiban.
Half life2 hours
Clearance
  • 213 – 314 mL/min [Healthy subjects]
  • 152 – 267 mL/min [patients with coronary artery disease]
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Tirofiban Action PathwayDrug actionSMP00267
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9934
Blood Brain Barrier + 0.5951
Caco-2 permeable - 0.6716
P-glycoprotein substrate Substrate 0.8571
P-glycoprotein inhibitor I Non-inhibitor 0.5443
P-glycoprotein inhibitor II Non-inhibitor 0.9898
Renal organic cation transporter Non-inhibitor 0.8435
CYP450 2C9 substrate Non-substrate 0.7483
CYP450 2D6 substrate Non-substrate 0.7803
CYP450 3A4 substrate Substrate 0.5096
CYP450 1A2 substrate Non-inhibitor 0.8569
CYP450 2C9 substrate Non-inhibitor 0.8219
CYP450 2D6 substrate Non-inhibitor 0.8967
CYP450 2C19 substrate Non-inhibitor 0.7916
CYP450 3A4 substrate Non-inhibitor 0.9023
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9498
Ames test Non AMES toxic 0.7023
Carcinogenicity Non-carcinogens 0.8449
Biodegradation Not ready biodegradable 0.9525
Rat acute toxicity 2.3684 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.5278
hERG inhibition (predictor II) Inhibitor 0.7024
Pharmacoeconomics
Manufacturers
  • Medicure international inc
Packagers
Dosage forms
FormRouteStrength
SolutionIntravenous
Prices
Unit descriptionCostUnit
Aggrastat 250 mcg/ml vial10.62USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States61367941999-01-292019-01-29
United States56589291993-09-272010-09-27
Canada22343642000-02-082016-10-23
Canada20520731998-05-262011-09-23
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubilityVery slightly solubleNot Available
logP1.4Not Available
Predicted Properties
PropertyValueSource
water solubility3.17e-03 g/lALOGPS
logP1.78ALOGPS
logP0.6ChemAxon
logS-5.1ALOGPS
pKa (strongest acidic)3.17ChemAxon
pKa (strongest basic)10.21ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count6ChemAxon
hydrogen donor count3ChemAxon
polar surface area104.73ChemAxon
rotatable bond count13ChemAxon
refractivity117.48ChemAxon
polarizability49.27ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

George Roby Thomas, Dawson James Reimer, Albert D. Friesen, “TRANSDERMAL PHARMACEUTICAL PREPARATION AND ADMINISTRATION OF TIROFIBAN.” U.S. Patent US20120029447, issued February 02, 2012.

US20120029447
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC07965
PubChem Compound60947
PubChem Substance46504678
ChemSpider54912
ChEBI9605
ChEMBLCHEMBL916
Therapeutic Targets DatabaseDAP000696
PharmGKBPA451698
HETAGG
Drug Product Database2240706
RxListhttp://www.rxlist.com/cgi/generic/tiro.htm
Drugs.comhttp://www.drugs.com/cdi/tirofiban.html
WikipediaTirofiban
ATC CodesB01AC17
AHFS Codes
  • 20:12.18
PDB EntriesNot Available
FDA labelshow(59.1 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AbciximabAdditive effects. Concomitant use is contraindicated.
EptifibatideAdditive effects. Concomitant use is contraindicated.
Ginkgo bilobaAdditive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
TreprostinilThe prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the antiplatelet agent, Tirofiban. Monitor for increased bleeding during concomitant thearpy.
Food InteractionsNot Available

Targets

1. Integrin alpha-IIb

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Integrin alpha-IIb P08514 Details

References:

  1. Theroux P, Alexander J Jr, Pharand C, Barr E, Snapinn S, Ghannam AF, Sax FL: Glycoprotein IIb/IIIa receptor blockade improves outcomes in diabetic patients presenting with unstable angina/non-ST-elevation myocardial infarction: results from the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) study. Circulation. 2000 Nov 14;102(20):2466-72. Pubmed
  2. Dickfeld T, Ruf A, Pogatsa-Murray G, Muller I, Engelmann B, Taubitz W, Fischer J, Meier O, Gawaz M: Differential antiplatelet effects of various glycoprotein IIb-IIIa antagonists. Thromb Res. 2001 Jan 15;101(2):53-64. Pubmed
  3. von Segesser LK, Mueller X, Marty B, Horisberger J, Corno A: Alternatives to unfractionated heparin for anticoagulation in cardiopulmonary bypass. Perfusion. 2001 Sep;16(5):411-6. Pubmed
  4. Kondo K, Umemura K: Clinical pharmacokinetics of tirofiban, a nonpeptide glycoprotein IIb/IIIa receptor antagonist: comparison with the monoclonal antibody abciximab. Clin Pharmacokinet. 2002;41(3):187-95. Pubmed
  5. Roffi M, Moliterno DJ, Meier B, Powers ER, Grines CL, DiBattiste PM, Herrmann HC, Bertrand M, Harris KE, Demopoulos LA, Topol EJ: Impact of different platelet glycoprotein IIb/IIIa receptor inhibitors among diabetic patients undergoing percutaneous coronary intervention: : Do Tirofiban and ReoPro Give Similar Efficacy Outcomes Trial (TARGET) 1-year follow-up. Circulation. 2002 Jun 11;105(23):2730-6. Pubmed
  6. Juwana YB, Suryapranata H, Ottervanger JP, van ’t Hof AW: Tirofiban for myocardial infarction. Expert Opin Pharmacother. 2010 Apr;11(5):861-6. Pubmed

2. Integrin beta-3

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Integrin beta-3 P05106 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. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed
  3. Juwana YB, Suryapranata H, Ottervanger JP, van ’t Hof AW: Tirofiban for myocardial infarction. Expert Opin Pharmacother. 2010 Apr;11(5):861-6. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on January 02, 2014 13:07