TIROFIBAN HYDROCHLORIDE ANHYDROUS

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H36N2O5S.ClH
Molecular Weight	477.058
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of TIROFIBAN HYDROCHLORIDE ANHYDROUS

Structure Search

SMILES

Cl.CCCCS(=O)(=O)N[C@@H](CC1=CC=C(OCCCCC2CCNCC2)C=C1)C(O)=O

InChI

InChIKey=KPKFFYOMPGOQRP-BOXHHOBZSA-N

InChI=1S/C22H36N2O5S.ClH/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);1H/t21-;/m0./s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/1998/20912lbl.pdf
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19343166 | https://www.ncbi.nlm.nih.gov/pubmed/9878994

Tirofiban is a non-peptide antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor. Tirofiban is a reversible, competitive inhibitor of GP IIb/IIIa receptors, exerting its effects via the prevention of the binding of fibrinogen and other ligands, resulting in the inhibition of the last common step of thrombi formation. Tirofiban was discovered by Merck, USA, and was approved by the FDA in 1998 under the trade name AGGRASTAT. AGGRASTAT, in combination with heparin, is indicated for the treatment of acute coronary syndrome, including patients who are to be managed medically and those undergoing percutaneous transluminal coronary angioplasty or atherectomy. AGGRASTAT reduces the risk of ischaemic complications in patients with unstable angina/non-Q-wave myocardial infarction and high-risk patients undergoing revascularisation when used against a background of heparin and aspirin. Furthermore, the drug has an acceptable tolerability profile. Therefore, intravenous tirofiban is likely to be used as an adjunct to heparin and aspirin in patients with acute coronary syndromes including high-risk patients undergoing revascularisation.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Integrin alpha-IIb/beta-3 14 Target ID: CHEMBL2093869 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19343166	Antagonist 2778		15.0 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acute coronary syndrome 33 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/1998/20912lbl.pdf	Primary		Approved 8429	AGGRASTAT Approved Use AGGRASTAT, in combination with heparin, is indicated for the treatment of acute coronary syndrome, including patients who are to be managed medically and those undergoing percutaneous transluminal coronary angioplasty or atherectomy. In this setting, AGGRASTAT has been shown to decrease the rate of a combined endpoint of death, new myocardial infarction or refractory ischemia/repeat cardiac procedure. Launch Date 1998

AUC

Value	Dose	Analyte	Population
193.4 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7955799/	0.15 μg/kg/min other, intravenous dose: 0.15 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered:	TIROFIBAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
209.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7955799/	0.2 μg/kg/min other, intravenous dose: 0.2 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered:	TIROFIBAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
92.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7955799/	0.1 μg/kg/min other, intravenous dose: 0.1 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered:	TIROFIBAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
1.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7955799/	0.15 μg/kg/min other, intravenous dose: 0.15 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered:	TIROFIBAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7955799/	0.2 μg/kg/min other, intravenous dose: 0.2 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered:	TIROFIBAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7955799/	0.1 μg/kg/min other, intravenous dose: 0.1 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered:	TIROFIBAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037	substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2C19 991 CYP1A2 1054

Drug as victim

Target	Modality	Activity
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10534322/ Page: -	no
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10534322/ Page: -	no
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10534322/ Page: -	yes
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10534322/ Page: -	yes
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10534322/ Page: -	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9605	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9605
ChemicalBook	CB9169083	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9169083
MolPort	MolPort-006-167-632	https://www.molport.com/shop/molecule-link/MolPort-006-167-632
ZINC	ZINC000003806104	http://zinc15.docking.org/substances/ZINC000003806104
eMolecules	6843975	https://www.emolecules.com/cgi-bin/more?vid=6843975

PubMed

Title	Date	PubMed
Bleeding risk of tirofiban, a nonpeptide GPIIb/IIIa platelet receptor antagonist in progressive stroke: an open pilot study.	2001	11721100
Safety and efficacy of thrombolysis with alteplase (50 mg) plus tirofiban versus alteplase (100 mg) alone in acute myocardial infarction: preliminary findings.	2001 Aug	11577835
Platelet glycoprotein IIb/IIIa-receptor inhibitors in patients with acute coronary syndromes or undergoing percutaneous coronary interventions: a review.	2001 Aug	11558855
GP IIb/IIIa inhibitors in coronary artery disease management: what the latest trials tell us.	2001 Dec	11765119
Cost implications of routine tirofiban use in the management of acute coronary syndromes.	2001 Dec	11744144
One-year experience with the platelet glycoprotein IIb/IIIa antagonist tirofiban and heparin during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia type II.	2001 Dec	11726910
Perioperative use of tirofiban hydrochloride (Aggrastat) does not increase surgical bleeding after emergency or urgent coronary artery bypass grafting.	2001 Dec	11726894
Treatment of acute basilar artery thrombosis with a combination of systemic alteplase and tirofiban, a nonpeptide platelet glycoprotein IIb/IIIa inhibitor: report of four cases.	2001 Dec	11719681
Standardized ultrasound as a new method to induce platelet aggregation: evaluation, influence of lipoproteins and of glycoprotein IIb/IIIa antagonist tirofiban.	2001 Dec	11704433
A risk stratification scheme for selection of a glycoprotein IIb/IIIa inhibitor during percutaneous coronary intervention based on clinical and angiographic criteria.	2001 Dec 1	11728356
Platelet inhibition after glycoprotein IIb/IIIa inhibitor therapy.	2001 Dec 18	11748127
Glycoprotein IIb/IIIa receptor blockers in acute coronary syndromes.	2001 Dec 8	11747950
Deep venous thrombosis prophylaxis is not indicated for laparoscopic cholecystectomy.	2001 Jul-Sep	11548825
Administration of abciximab to patients receiving tirofiban or eptifibatide: effect on platelet function.	2001 Mar 1	11693761
Augmentation of in-vitro clot dissolution by low frequency high-intensity ultrasound combined with antiplatelet and antithrombotic drugs.	2001 May	11577261
Elevation in serum troponin I predicts the benefit of tirofiban.	2001 May	11577259
Short-term comparative outcomes associated with the use of GP IIb/IIIa antagonists in patients undergoing coronary intervention.	2001 May	11577258
[Indications for intravenous GPIIb/IIIa receptor inhibitors in acute coronary syndrome without prolonged ST syndrome].	2001 Nov	11794966
Small peptide GP IIb/IIIa receptor inhibitors as upstream therapy in non-ST-segment elevation acute coronary syndromes: results of the PURSUIT, PRISM, PRISM-PLUS, TACTICS, and PARAGON trials.	2001 Nov	11704707
ESPRIT in context: pharmacology matters!	2001 Nov	11603901
[Rescue thrombectomy after stent implantation in a degenerating aortocoronary bypass].	2001 Nov 15	11760656
Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes.	2001 Nov 22	11794229
Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes.	2001 Nov 22	11794228
Acute coronary syndrome without ST elevation: implementation of new guidelines.	2001 Nov 3	11705583
Intravenous glycoprotein IIb/IIIa inhibition in non-ST segment elevation acute coronary syndromes.	2001 Nov-Dec	11727277
Comparison of GP IIB/IIIA inhibitors and their activity as measured by aggregometry, flow cytometry, single platelet counting, and the rapid platelet function analyzer.	2001 Oct	11729364
Differential effects of citrate versus PPACK anticoagulation on measured platelet inhibition by abciximab, eptifibatide and tirofiban.	2001 Oct	11729363
[Comparison of 2 platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization].	2001 Oct	11723620
[Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban].	2001 Oct	11723619
Increased reperfusion by glycoprotein IIb/IIIa receptor antagonist administration in case of unsuccessful and failed thrombolysis in patients with acute myocardial infarction: a pilot study.	2001 Oct	11721719
A comparison of total hospital costs for percutaneous coronary intervention patients receiving abciximab versus tirofiban.	2001 Oct	11590674
Stability of tirofiban hydrochloride in 0.9% sodium chloride injection for 30 days.	2001 Oct 1	11596703
Effects of clopidogrel pretreatment before percutaneous coronary intervention in patients treated with glycoprotein IIb/IIIa inhibitors (abciximab or tirofiban).	2001 Oct 15	11676953
Use of coronary revascularization in patients with unstable and non-ST-segment elevation acute myocardial infarction.	2001 Oct 18	11694216
Interpreting new treatment guidelines for non-ST-segment elevation acute coronary syndromes.	2001 Oct 18	11694215
[Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization].	2001 Sep	11763604
Should patients with unstable coronary syndromes routinely undergo cardiac catheterization and appropriate revascularization?	2001 Sep	11674901
ReoPro rules: results from the 'Do Tirofiban and ReoPro Give Similar Efficacy Trial' (TARGET).	2001 Sep	11585028
Resolution of a spontaneous coronary artery thrombus with a new antiplatelet agent.	2001 Sep	11573060
Alternatives to unfractionated heparin for anticoagulation in cardiopulmonary bypass.	2001 Sep	11565896
Pharmacodynamic characterization of the interaction between abciximab or tirofiban with unfractionated or a low molecular weight heparin in healthy subjects.	2001 Sep	11560562
Tirofiban therapy does not increase the risk of hemorrhage after emergency coronary surgery.	2001 Sep	11547328
Adjunctive therapies in the cath lab. Use of combination glycoprotein IIb/IIIa inhibitor and direct thrombin inhibitor drugs to support percutaneous coronary stent placement in a patient with renal insufficiency and heparin-induced thrombocytopenia.	2001 Sep	11533507
Adjunctive therapies in the cath lab. Intracoronary tirofiban infusion in a case with massive intracoronary thrombus.	2001 Sep	11533506
Dissociation of glycoprotein IIb/IIIa antagonists from platelets does not result in fibrinogen binding or platelet aggregation.	2001 Sep 18	11560852
Oral glycoprotein IIb/IIa antagonists for unstable angina--is there still a chance for the oral substances?	2001 Sep 30	11567679
The role of glycoprotein IIb/IIIa inhibition in the management of acute coronary syndromes.	2001 Sep-Oct	11604974
Prior aspirin use in unstable angina predisposes to higher risk: the aspirin paradox.	2001 Sep-Oct	11578715
An integrated clinical approach to predicting the benefit of tirofiban in non-ST elevation acute coronary syndromes. Application of the TIMI Risk Score for UA/NSTEMI in PRISM-PLUS.	2002 Feb	11792137
Cost effectiveness of invasive strategy in unstable coronary disease--what are we waiting for?	2002 Jan	11741352

Patents

Sample Use Guides

In Vivo Use Guide

In most patients, AGGRASTAT should be administered intravenously, at an initial rate of 0.4 µg/kg/min for 30 minutes and then continued at 0.1 µg/kg/min. Patients with severe renal insufficiency (creatinine clearance <30 mL/min) should receive half the usual rate of infusion.

Route of Administration: Intravenous

In Vitro Use Guide

Platelet-rich plasma from each subject was incubated in vitro with increasing concentrations of tirofiban (25, 37.5, and 50ng/ml), patients with moderate to severe renal dysfunction suppress their platelet aggregation to <10% with 25ng/ml of tirofiban, one-third of the standard effective dose for patients with normal renal function.

Name

Type

Language

TIROFIBAN HYDROCHLORIDE ANHYDROUS

Common Name

English

L-TYROSINE, N-(BUTYLSULFONYL)-O-(4-(4-PIPERIDINYL)BUTYL)-, HYDROCHLORIDE (1:1)

Systematic Name

English

L-TYROSINE, N-(BUTYLSULFONYL)-O-(4-(4-PIPERIDINYL)BUTYL)-, MONOHYDROCHLORIDE

Common Name

English

TIROFIBAN HYDROCHLORIDE ANHYDROUS [MI]

Common Name

English

Tirofiban hydrochloride [WHO-DD]

Common Name

English

Code System Code Type Description

PUBCHEM

64781