Tirofiban

Identification

Name
Tirofiban
Accession Number
DB00775
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.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 440.597
Monoisotopic: 440.234492962
Chemical Formula
C22H36N2O5S
Synonyms
  • (2S)-2-(butylsulfonylamino)-3-[4-(4-piperidin-4-ylbutoxy)phenyl]propanoic acid
  • N-(Butylsulfonyl)-O-(4-(4-piperidyl)butyl)-L-tyrosine
  • Tirofiban
  • Tirofibán
  • Tirofibanum
External IDs
  • MK 383

Pharmacology

Indication

For treatment, in combination with heparin, of acute coronary syndrome, including patients who are to be managed medically and those undergoing PTCA or atherectomy.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

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 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 action

Tirofiban 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.

TargetActionsOrganism
AIntegrin alpha-IIb
antagonist
Humans
AIntegrin beta-3
antagonist
Humans
Absorption
Not Available
Volume of distribution
  • 22 to 42 L
Protein binding

65%

Metabolism

Metabolism appears to be limited.

Route of elimination

It 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-life

2 hours

Clearance
  • 213 - 314 mL/min [Healthy subjects]
  • 152 - 267 mL/min [patients with coronary artery disease]
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Tirofiban Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirTirofiban may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbciximabThe risk or severity of bleeding can be increased when Tirofiban is combined with Abciximab.
AcarboseAcarbose may decrease the excretion rate of Tirofiban which could result in a higher serum level.
AceclofenacThe risk or severity of bleeding can be increased when Aceclofenac is combined with Tirofiban.
AcemetacinThe risk or severity of bleeding can be increased when Acemetacin is combined with Tirofiban.
AcenocoumarolThe risk or severity of bleeding can be increased when Tirofiban is combined with Acenocoumarol.
AcetaminophenAcetaminophen may decrease the excretion rate of Tirofiban which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Tirofiban which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may increase the antiplatelet activities of Tirofiban.
AclidiniumTirofiban may decrease the excretion rate of Aclidinium which could result in a higher serum level.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
No interactions found.

Products

Product Ingredients
IngredientUNIICASInChI Key
Tirofiban hydrochloride6H925F8O5J150915-40-5HWAAPJPFZPHHBC-FGJQBABTSA-N
International/Other Brands
Aggribloc (Abbott) / Agrastat (Merck Sharp & Dohme)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AggrastatLiquidIntravenousCorrevio (Uk) Ltd1999-09-162013-02-06Canada flag
AggrastatInjection, solution5 mg/100mLIntravenousMedicure International Inc1998-05-14Not applicableUS flag
AggrastatSolutionIntravenousCipher Pharmaceuticals Inc.2002-05-01Not applicableCanada flag
AggrastatInjection, solution3.75 mg/15mLIntravenousMedicure International Inc2016-10-15Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more

Categories

ATC Codes
B01AC17 — Tirofiban
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenylalanine and derivatives. These are compounds containing phenylalanine or a derivative thereof resulting from reaction of phenylalanine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Phenylalanine and derivatives
Alternative Parents
Phenylpropanoic acids / Amphetamines and derivatives / Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Piperidines / Organosulfonamides / Organic sulfonamides / Aminosulfonyl compounds / Amino acids
show 8 more
Substituents
3-phenylpropanoic-acid / Alkyl aryl ether / Amine / Amino acid / Aminosulfonyl compound / Amphetamine or derivatives / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Carbonyl group
show 24 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
piperidines, sulfonamide, L-tyrosine derivative (CHEBI:9605)

Chemical Identifiers

UNII
GGX234SI5H
CAS number
144494-65-5
InChI Key
COKMIXFXJJXBQG-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[[email protected]@H](CC1=CC=C(OCCCCC2CCNCC2)C=C1)C(O)=O

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 References
Not Available
Human Metabolome Database
HMDB0014913
KEGG Compound
C07965
PubChem Compound
60947
PubChem Substance
46504678
ChemSpider
54912
BindingDB
50004058
RxNav
73137
ChEBI
9605
ChEMBL
CHEMBL916
ZINC
ZINC000003806104
Therapeutic Targets Database
DAP000696
PharmGKB
PA451698
PDBe Ligand
AGG
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Tirofiban
AHFS Codes
  • 20:12.18 — Platelet Aggregation Inhibitors
PDB Entries
2vdm
FDA label
Download (59.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentAcute Coronary Syndromes (ACS)1
4CompletedTreatmentAcute Myocardial Infarction (AMI)3
4CompletedTreatmentAcute Myocardial Infarction (AMI) / Percutaneous Coronary Intervention (PCI)1
4CompletedTreatmentAngioplasty, Transluminal, Percutaneous Coronary1
4CompletedTreatmentCoronary Artery Disease (CAD)2
4CompletedTreatmentCoronary Artery Disease (CAD) / ST Elevation Myocardial Infarction (STEMI)1
4CompletedTreatmentMyocardial Infarction / Percutaneous Coronary Intervention (PCI) / Thrombolytic Therapy1
4CompletedTreatmentNo-Reflow Phenomenon1
4CompletedTreatmentNon-ST Elevation Myocardial Infarction1
4RecruitingTreatmentST Elevation Myocardial Infarction / ST Elevation Myocardial Infarction (STEMI)1

Pharmacoeconomics

Manufacturers
  • Medicure international inc
Packagers
  • Baxter International Inc.
  • Ben Venue Laboratories Inc.
  • Guilford Pharmaceuticals
  • Iroko Pharmaceuticals
  • Medicure International Inc.
  • Merck & Co.
Dosage Forms
FormRouteStrength
Injection, solutionIntravenous0.05 MG/ML
Injection, solutionIntravenous3.75 mg/15mL
Injection, solutionIntravenous5 mg/100mL
Injection, solution, concentrateIntravenous250 mcg/1mL
Injection, solution, concentrateIntravenous; Parenteral250 MICROGRAMMI/ML
LiquidIntravenous
SolutionIntravenous
Injection, solution, concentrateParenteral250 Mikrogramm/ml
SolutionParenteral50 Mikrogramm/ml
Injection, solution, concentrateIntravenous12.5 mg/50ml
Injection, solutionIntravenous50 mcg/ml
SolutionIntravenous50 mcg/ml
Solution, concentrateIntravenous0.25 mg
InjectionNot applicable0.25 mg/1mL
Injection, solutionParenteral50 MICROGRAMMI/ML
InjectionIntravenous12.5 mg/50ml
Prices
Unit descriptionCostUnit
Aggrastat 250 mcg/ml vial10.62USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5658929No1997-08-192010-09-27US flag
CA2234364No2000-02-082016-10-23Canada flag
CA2052073No1998-05-262011-09-23Canada flag
US6770660No2004-08-032023-05-01US flag
US5965581No1999-10-122016-10-23US flag
US5978698No1999-11-022017-10-08US flag
US5733919No1998-03-312016-10-23US flag
US5972967No1999-10-262016-10-23US flag
US6136794No2000-10-242019-01-29US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityVery slightly solubleNot Available
logP1.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00317 mg/mLALOGPS
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 Area104.73 Å2ChemAxon
Rotatable Bond Count13ChemAxon
Refractivity117.48 m3·mol-1ChemAxon
Polarizability49.27 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9934
Blood Brain Barrier+0.5951
Caco-2 permeable-0.6716
P-glycoprotein substrateSubstrate0.8571
P-glycoprotein inhibitor INon-inhibitor0.5443
P-glycoprotein inhibitor IINon-inhibitor0.9898
Renal organic cation transporterNon-inhibitor0.8435
CYP450 2C9 substrateNon-substrate0.7483
CYP450 2D6 substrateNon-substrate0.7803
CYP450 3A4 substrateSubstrate0.5096
CYP450 1A2 substrateNon-inhibitor0.8569
CYP450 2C9 inhibitorNon-inhibitor0.8219
CYP450 2D6 inhibitorNon-inhibitor0.8967
CYP450 2C19 inhibitorNon-inhibitor0.7916
CYP450 3A4 inhibitorNon-inhibitor0.9023
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9498
Ames testNon AMES toxic0.7023
CarcinogenicityNon-carcinogens0.8449
BiodegradationNot ready biodegradable0.9525
Rat acute toxicity2.3684 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5278
hERG inhibition (predictor II)Inhibitor0.7024
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

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Metal ion binding
Specific Function
Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recogn...
Gene Name
ITGA2B
Uniprot ID
P08514
Uniprot Name
Integrin alpha-IIb
Molecular Weight
113375.96 Da
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:11076818]
  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:11342206]
  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:11565896]
  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:11929319]
  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:12057986]
  6. Juwana YB, Suryapranata H, Ottervanger JP, van 't Hof AW: Tirofiban for myocardial infarction. Expert Opin Pharmacother. 2010 Apr;11(5):861-6. doi: 10.1517/14656561003690005. [PubMed:20210689]
Details
2. Integrin beta-3
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Wil...
Gene Name
ITGB3
Uniprot ID
P05106
Uniprot Name
Integrin beta-3
Molecular Weight
87056.975 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  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:10592235]
  3. Juwana YB, Suryapranata H, Ottervanger JP, van 't Hof AW: Tirofiban for myocardial infarction. Expert Opin Pharmacother. 2010 Apr;11(5):861-6. doi: 10.1517/14656561003690005. [PubMed:20210689]

Drug created on June 13, 2005 07:24 / Updated on October 23, 2020 21:53

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates