Identification
- Summary
Argatroban is a synthetic direct thrombin inhibitor used for the prevention and treatment of thrombosis related to heparin use.
- Generic Name
- Argatroban
- DrugBank Accession Number
- DB00278
- Background
Argatroban is a direct, selective thrombin inhibitor. The American College of Cardiologists (ACC) recommend using bivalirudin or argatroban in patients who have had, or at risk for, heparin induced thrombocytopenia (HIT) and are undergoing percutaneous coronary intervention. Argatroban is a non-heparin anticoagulant shown to both normalize platelet count in patients with HIT and prevent the formation of thrombi. Parental anticoagulants must be stopped and a baseline activated partial thromboplastin time must be obtained prior to administering argatroban.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Argatroban (DB00278)
- Weight
- Average: 508.64
Monoisotopic: 508.246789457 - Chemical Formula
- C23H36N6O5S
- Synonyms
- Argatroban
- Argatroban anhydrous
Pharmacology
- Indication
Argatroban is indicated for prevention and treatment of thrombosis caused by heparin-induced thrombocytopenia (HIT). It is also indicated for use in patients with, or at risk for, HIT who are undergoing percutaneous coronary intervention.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Prophylaxis of Thrombosis •••••••••••• ••••• •••••••••••• •••••••• •••••••••••• ••••• Treatment of Thrombosis •••••••••••• •••••• Prophylaxis of Thrombosis •••••••••••• ••••• - Contraindications & Blackbox Warnings
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Argatroban is a synthetic direct thrombin inhibitor derived from L-arginine indicated as an anticoagulant for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia. Argatroban is a direct thrombin inhibitor that reversibly binds to the thrombin active site. Argatroban does not require the co-factor antithrombin III for antithrombotic activity. Argatroban exerts its anticoagulant effects by inhibiting thrombin-catalyzed or -induced reactions, including fibrin formation; activation of coagulation factors V, VIII, and XIII; protein C; and platelet aggregation. Argatroban is highly selective for thrombin with an inhibitory constant (Ki) of 0.04 µM. At therapeutic concentrations, Argatroban has little or no effect on related serine proteases (trypsin, factor Xa, plasmin, and kallikrein). Argatroban is capable of inhibiting the action of both free and clot-associated thrombin.
- Mechanism of action
Argatroban exerts its anticoagulant effects by inhibiting thrombin-catalyzed or -induced reactions, including fibrin formation; activation of coagulation factors V, VIII, and XIII; protein C; and platelet aggregation.
Target Actions Organism AProthrombin inhibitorHumans - Absorption
Bioavailability is 100% (intravenous).
- Volume of distribution
- 174 mL/kg
- 12.18 L [70-kg adult]
- Protein binding
54%
- Metabolism
Liver via hydroxylation and aromatization of the 3-methyltetrahydroquinoline ring. Age and gender do not substantially affect the pharmacodynamic or pharmacokinetic profile of argatroban.
- Route of elimination
Argatroban is excreted primarily in the feces (65%), presumably through biliary secretion; 22% is eliminated via urine.
- Half-life
39 and 51 minutes
- Clearance
- 5.1 L/kg/hr [infusion doses up to 40 mcg/kg/min]
- Adverse Effects
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Excessive bleeding
- Pathways
Pathway Category Argatroban Action Pathway Drug action - Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The risk or severity of bleeding can be increased when Abciximab is combined with Argatroban. Aceclofenac The risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Argatroban. Acemetacin The risk or severity of bleeding and hemorrhage can be increased when Argatroban is combined with Acemetacin. Acenocoumarol The risk or severity of bleeding can be increased when Argatroban is combined with Acenocoumarol. Acetylsalicylic acid Acetylsalicylic acid may increase the anticoagulant activities of Argatroban. - Food Interactions
- Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
- Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of argatroban; however, the evidence is conflicting.
- Exercise caution with St. John's Wort.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Argatroban monohydrate IY90U61Z3S 141396-28-3 AIEZTKLTLCMZIA-CZSXTPSTSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Argatroban Solution 100 mg / mL Intravenous Sandoz Canada Incorporated 2002-06-13 Not applicable Canada 
Argatroban Injection, solution 1 mg/1mL Intravenous Teva Parenteral Medicines, Inc. 2015-04-27 2017-03-31 US 
Argatroban Injection 250 mg/2.5mL Intravenous Hikma Pharmaceuticals USA Inc. 2012-01-05 Not applicable US Argatroban Injection 1 mg/1mL Intravenous Sandoz Inc 2011-09-06 Not applicable US Argatroban Injection 1 mg/1mL Intravenous Eagle Pharmaceuticals, Inc. 2011-09-06 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Argatroban Injection 50 mg/50mL Intravenous Fresenius Kabi USA, LLC 2021-05-24 Not applicable US Argatroban Injection, solution 250 mg/2.5mL Intravenous Mylan Institutional LLC 2017-11-14 Not applicable US Argatroban Injection 250 mg/2.5mL Intravenous Par Pharmaceutical, Inc. 2015-06-01 Not applicable US Argatroban Injection, solution 1 mg/1mL Intravenous Sagent Pharmaceuticals 2021-04-15 Not applicable US Argatroban Injection, solution 100 mg/1mL Intravenous Hospira, Inc. 2017-03-06 Not applicable US
Categories
- ATC Codes
- B01AE03 — Argatroban
- Drug Categories
- Amides
- Amino Acids
- Amino Acids, Basic
- Amino Acids, Diamino
- Amino Acids, Essential
- Amino Acids, Peptides, and Proteins
- Anticoagulants
- Antithrombins
- Blood and Blood Forming Organs
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Substrates
- Enzyme Inhibitors
- Hematologic Agents
- Narrow Therapeutic Index Drugs
- Piperidines
- Protease Inhibitors
- Serine Protease Inhibitors
- Sulfones
- Sulfur Compounds
- Thrombin Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Dipeptides
- Alternative Parents
- Alpha amino acid amides / Hydroquinolines / Piperidinecarboxylic acids / N-acylpiperidines / Secondary alkylarylamines / Aralkylamines / Organosulfonamides / Benzenoids / Tertiary carboxylic acid amides / Aminosulfonyl compounds show 11 more
- Substituents
- Alpha-amino acid amide / Alpha-amino acid or derivatives / Alpha-dipeptide / Amine / Amino acid / Amino acid or derivatives / Aminosulfonyl compound / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle show 28 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- OCY3U280Y3
- CAS number
- 74863-84-6
- InChI Key
- KXNPVXPOPUZYGB-IOVMHBDKSA-N
- InChI
- InChI=1S/C23H36N6O5S/c1-14-8-10-29(18(12-14)22(31)32)21(30)17(6-4-9-26-23(24)25)28-35(33,34)19-7-3-5-16-11-15(2)13-27-20(16)19/h3,5,7,14-15,17-18,27-28H,4,6,8-13H2,1-2H3,(H,31,32)(H4,24,25,26)/t14-,15?,17+,18-/m1/s1
- IUPAC Name
- (2R,4R)-1-[(2S)-5-carbamimidamido-2-(3-methyl-1,2,3,4-tetrahydroquinoline-8-sulfonamido)pentanoyl]-4-methylpiperidine-2-carboxylic acid
- SMILES
- C[C@@H]1CCN([C@H](C1)C(O)=O)C(=O)[C@H](CCCNC(N)=N)NS(=O)(=O)C1=CC=CC2=C1NCC(C)C2
References
- Synthesis Reference
Tomiya Mano, Jin Shiomura, "Argatroban preparations for ophthalmic use." U.S. Patent US5506241, issued October, 1986.
US5506241- General References
- Di Nisio M, Middeldorp S, Buller HR: Direct thrombin inhibitors. N Engl J Med. 2005 Sep 8;353(10):1028-40. [Article]
- External Links
- Human Metabolome Database
- HMDB0014423
- KEGG Compound
- C04931
- PubChem Compound
- 152951
- PubChem Substance
- 46507650
- ChemSpider
- 83702
- BindingDB
- 50038001
- 15202
- ChEBI
- 94385
- ChEMBL
- CHEMBL1166
- Therapeutic Targets Database
- DAP000758
- PharmGKB
- PA164745516
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Argatroban
- FDA label
- Download (83.7 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Acute Progressive Ischemic Stroke 1 4 Completed Treatment CVD 2 4 Completed Treatment End Stage Renal Disease (ESRD) / Renal Failure, Chronic Renal Failure 1 4 Completed Treatment Ischemic Stroke 1 4 Completed Treatment Stable Coronary Artery Disease (CAD) / Unstable Angina (Troponin Negative) 1
Pharmacoeconomics
- Manufacturers
- Pfizer inc
- Packagers
- GlaxoSmithKline Inc.
- Dosage Forms
Form Route Strength Solution Parenteral 1 mg/ml Injection, solution, concentrate Intravenous 100 mg/ml Injection Intravenous 1 mg/1mL Injection Intravenous 250 mg/2.5mL Injection Intravenous 50 mg/50mL Injection, solution Intravenous 1 mg/1mL Injection, solution Intravenous 100 mg/1mL Injection, solution Intravenous 250 mg/2.5mL Injection, solution Intravenous 50 mg/50mL Solution Intravenous 100 mg / mL Solution Intravenous 125 mg/125mL Solution Parenteral Injection, solution, concentrate Intravenous; Parenteral 100 MG/ML - Prices
Unit description Cost Unit Argatroban 100 mg/ml Solution 2.5ml Vial 1546.46USD vial Argatroban 100 mg/ml vial 743.49USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5214052 No 1993-05-25 2014-06-30 US US7589106 No 2009-09-15 2027-09-26 US US7687516 No 2010-03-30 2027-09-26 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source logP 1 Not Available - Predicted Properties
Property Value Source Water Solubility 0.168 mg/mL ALOGPS logP 0.04 ALOGPS logP -0.92 Chemaxon logS -3.5 ALOGPS pKa (Strongest Acidic) 3.06 Chemaxon pKa (Strongest Basic) 11.8 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 9 Chemaxon Hydrogen Donor Count 6 Chemaxon Polar Surface Area 177.71 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 143.83 m3·mol-1 Chemaxon Polarizability 53.77 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.6195 Blood Brain Barrier - 0.8933 Caco-2 permeable - 0.7293 P-glycoprotein substrate Substrate 0.8193 P-glycoprotein inhibitor I Non-inhibitor 0.6701 P-glycoprotein inhibitor II Non-inhibitor 0.6802 Renal organic cation transporter Non-inhibitor 0.8147 CYP450 2C9 substrate Non-substrate 0.5571 CYP450 2D6 substrate Non-substrate 0.8861 CYP450 3A4 substrate Non-substrate 0.5477 CYP450 1A2 substrate Non-inhibitor 0.8849 CYP450 2C9 inhibitor Non-inhibitor 0.662 CYP450 2D6 inhibitor Non-inhibitor 0.8789 CYP450 2C19 inhibitor Non-inhibitor 0.7706 CYP450 3A4 inhibitor Non-inhibitor 0.8316 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9636 Ames test Non AMES toxic 0.6238 Carcinogenicity Non-carcinogens 0.7551 Biodegradation Not ready biodegradable 0.9966 Rat acute toxicity 1.5767 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9833 hERG inhibition (predictor II) Non-inhibitor 0.6071
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Thrombospondin receptor activity
- Specific Function
- Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostas...
- Gene Name
- F2
- Uniprot ID
- P00734
- Uniprot Name
- Prothrombin
- Molecular Weight
- 70036.295 Da
References
- Kawada T, Okada Y, Hoson M, Endo S, Yokoyama M, Kitanaka Y, Kimura K, Abe H, Yamate N: Argatroban, an attractive anticoagulant, for left heart bypass with centrifugal pump for repair of traumatic aortic rupture. Jpn J Thorac Cardiovasc Surg. 1999 Mar;47(3):104-9. [Article]
- Sakai M, Ohteki H, Narita Y, Naitoh K, Natsuaki M, Itoh T: Argatroban as a potential anticoagulant in cardiopulmonary bypass-studies in a dog model. Cardiovasc Surg. 1999 Mar;7(2):187-94. [Article]
- Jang IK, Brown DF, Giugliano RP, Anderson HV, Losordo D, Nicolau JC, Dutra OP, Bazzino O, Viamonte VM, Norbady R, Liprandi AS, Massey TJ, Dinsmore R, Schwarz RP Jr: A multicenter, randomized study of argatroban versus heparin as adjunct to tissue plasminogen activator (TPA) in acute myocardial infarction: myocardial infarction with novastan and TPA (MINT) study. J Am Coll Cardiol. 1999 Jun;33(7):1879-85. [Article]
- Matsuo T, Kario K, Matsuda S, Yamaguchi N, Kakishita E: Effect of Thrombin Inhibition on Patients with Peripheral Arterial Obstructive Disease: A Multicenter Clinical Trial of Argatroban. J Thromb Thrombolysis. 1995;2(2):131-136. [Article]
- Serebruany VL, Jang IK, Giugliano RP, Massey TJ, Schwarz Jr RP: A Randomized, Blinded Study of Two Doses of Novastan(R) (Brand of Argatroban) Versus Heparin as Adjunctive Therapy to Recombinant Tissue Plasminogen Activator (Accelerated Administration) in Acute Myocardial Infarction: Rationale and Design of the Myocardial Infarction using Novastan(R) and T-PA (MINT) Study. J Thromb Thrombolysis. 1998;5(1):49-52. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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 react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Tran JQ, Di Cicco RA, Sheth SB, Tucci M, Peng L, Jorkasky DK, Hursting MJ, Benincosa LJ: Assessment of the potential pharmacokinetic and pharmacodynamic interactions between erythromycin and argatroban. J Clin Pharmacol. 1999 May;39(5):513-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxygen binding
- 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 un...
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Tran JQ, Di Cicco RA, Sheth SB, Tucci M, Peng L, Jorkasky DK, Hursting MJ, Benincosa LJ: Assessment of the potential pharmacokinetic and pharmacodynamic interactions between erythromycin and argatroban. J Clin Pharmacol. 1999 May;39(5):513-9. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Not Available
- Specific Function
- Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Components:
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54