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Identification
NameBivalirudin
Accession NumberDB00006  (BIOD00076, BTD00076)
TypeBiotech
GroupsApproved, Investigational
Description

Bivalirudin is a synthetic 20 residue peptide (thrombin inhibitor) which reversibly inhibits thrombin. Once bound to the active site, thrombin cannot activate fibrinogen into fibrin, the crucial step in the formation of thrombus. It is administered intravenously. Because it can cause blood stagnation, it is important to monitor changes in hematocrit, activated partial thromboplastin time, international normalized ratio and blood pressure.

Protein structureNo structure small
Protein chemical formulaC98H138N24O33
Protein average weight2180.2853
Sequences
>Bivalirudin sequence
FPRPGGGGNGDFEEIPEEYL
Download FASTA Format
SynonymsNot Available
SaltsNot Available
Brand names
NameCompany
AngiomaxMedicines Co or MDCO
AngioxNot Available
Brand mixturesNot Available
Categories
CAS number128270-60-0
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentPeptides
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationFor treatment of heparin-induced thrombocytopenia and for the prevention of thrombosis. Bivalirudin is indicated for use in patients undergoing percutaneous coronary intervention (PCI), in patients at moderate to high risk acute coronary syndromes due to unstable angina or non-ST segment elevation in whom a PCI is planned.
PharmacodynamicsBivalirudin directly and reversibly inhibits thrombin by specifically binding both to the catalytic site and to the anion-binding exosite of circulating and clot-bound thrombin. The action of bivalirudin is reversible because thrombin will slowly cleave the thrombin-bivalirudin bond which recovers the active site of thrombin.
Mechanism of actionInhibits the action of thrombin by binding both to its catalytic site and to its anion-binding exosite. Thrombin is a serine proteinase that plays a central role in the thrombotic process, acting to cleave fibrinogen into fibrin monomers and to activate Factor XIII to Factor XIIIa, allowing fibrin to develop a covalently cross-linked framework which stabilizes the thrombus; thrombin also activates Factors V and VIII, promoting further thrombin generation, and activates platelets, stimulating aggregation and granule release.
AbsorptionFollowing intravenous administration, bivalirudin exhibits linear pharmacokinetics . The mean steady state concentration is 12.3 +/- 1.7mcg/mL after administration of an intravenous bolus of 1mg/kg followd by a 2.5mg/kg/hr intravenous infusion given over 4 hours.
Volume of distribution

0.2L/kg

Protein bindingOther than thrombin and red blood cells, bivalirudin does not bind to plasma proteins.
Metabolism

80% proteolytic cleavage

Route of eliminationBivalirudin is cleared from plasma by a combination of renal mechanisms (20%) and proteolytic cleavage.
Half life* Normal renal function: 25 min (in normal conditions) * Creatinine clearance 10-29mL/min: 57min * Dialysis-dependant patients: 3.5h
Clearance
  • 3.4 mL/min/kg [Normal renal function]
  • 3.4 mL/min/kg [mild renal function]
  • 2.7 mL/min/kg [moderate renal function]
  • 2.8 mL/min/kg [severe renal function]
  • 1 mL/min/kg [Dialysis-dependent patients]
ToxicityBased on a study by Gleason et al., the no-observed-adverse-effect level (NOAEL) for bivalirudin, administered to rats via intravenous infusion over a 24-hour period, was 2000 mg/kg/24 h.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Bivalirudin Action PathwayDrug actionSMP00277
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
Manufacturers
  • The medicines co
Packagers
Dosage forms
FormRouteStrength
Powder, for solutionIntravenous250mg
Prices
Unit descriptionCostUnit
Angiomax 250 mg vial780.0USDvial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States75827272009-01-272029-01-27
United States51964041993-05-232010-05-23
Canada20651501999-12-142010-08-17
Properties
Stateliquid
Experimental Properties
PropertyValueSource
hydrophobicity-0.985Not Available
isoelectric point3.91Not Available
References
Synthesis Reference

Avi Tovi, Chaim Eidelman, Shimon Shushan, Alon Hagi, Alexander Ivchenko, Gabriel-Marcus Butilca, Leah Bar-Oz, Tehila Gadi, Gil Zaovi, “Process for production of Bivalirudin.” U.S. Patent US20070093423, issued April 26, 2007.

US20070093423
General Reference
  1. Seybert AL, Coons JC, Zerumsky K: Treatment of heparin-induced thrombocytopenia: is there a role for bivalirudin? Pharmacotherapy. 2006 Feb;26(2):229-41. Pubmed
  2. Dager WE, Dougherty JA, Nguyen PH, Militello MA, Smythe MA: Heparin-induced thrombocytopenia: treatment options and special considerations. Pharmacotherapy. 2007 Apr;27(4):564-87. Pubmed
  3. Dang CH, Durkalski VL, Nappi JM: Evaluation of treatment with direct thrombin inhibitors in patients with heparin-induced thrombocytopenia. Pharmacotherapy. 2006 Apr;26(4):461-8. Pubmed
  4. Robson R: The use of bivalirudin in patients with renal impairment. J Invasive Cardiol. 2000 Dec;12 Suppl F:33F-6. Pubmed
  5. Van De Car DA, Rao SV, Ohman EM: Bivalirudin: a review of the pharmacology and clinical application. Expert Rev Cardiovasc Ther. 2010 Dec;8(12):1673-81. Pubmed
  6. Shammas NW: Bivalirudin: pharmacology and clinical applications. Cardiovasc Drug Rev. 2005 Winter;23(4):345-60. Pubmed
  7. Gleason TG, Chengelis CP, Jackson CB, Lindstrom P: A 24-hour continuous infusion study of bivalirudin in the rat. Int J Toxicol. 2003 May-Jun;22(3):195-206. Pubmed
External Links
ResourceLink
PharmGKBPA10032
Drug Product Database2246533
RxListhttp://www.rxlist.com/cgi/generic/angiomax.htm
Drugs.comhttp://www.drugs.com/cdi/bivalirudin.html
WikipediaBivalirudin
ATC CodesB01AE06
AHFS Codes
  • 20:12.04.12
PDB Entries
FDA labelshow(60.4 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
DeferasiroxAnticoagulants increase the risk for gastrointestinal ulceration/irritation and/or GI bleeding. If these two agents must be used, patients need to be closely monitored for signs and symptoms of GI toxicity.
GemcitabineGemcitabine may enhance the adverse/toxic effect of Bleomycin. The risk of pulmonary toxicity may be increased. Use extreme caution if using gemcitabine and bleomycin in combination. Monitor for the development of pulmonary toxicity.
Ginkgo bilobaAdditive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
RivaroxabanAnticoagulants may enhance the anticoagulant effect of rivaroxaban. Avoid concurrent use of rivaroxaban with other anticoagulants whenever possible, other than during transition periods, due to the possible increased for bleeding.
TreprostinilThe prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the anticoagulant, Bivalirudin. Monitor for increased bleeding during concomitant thearpy.
Food Interactions
  • Dan shen, dong quai, evening primrose oil, gingko, policosanol, willow bark
  • Echinacea

Targets

1. Prothrombin

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Prothrombin P00734 Details

References:

  1. Scatena R: Bivalirudin: a new generation antithrombotic drug. Expert Opin Investig Drugs. 2000 May;9(5):1119-27. Pubmed
  2. Bates ER: Bivalirudin for percutaneous coronary intervention and in acute coronary syndromes. Curr Cardiol Rep. 2001 Sep;3(5):348-54. Pubmed
  3. Gladwell TD: Bivalirudin: a direct thrombin inhibitor. Clin Ther. 2002 Jan;24(1):38-58. Pubmed
  4. Kleiman NS, Klem J, Fernandes LS, Rubin H, Challa S, Solomon S, Maresh K, Arora U, Klem E, Buergler J, Mathew S, Browning A, DeLao T: Pharmacodynamic profile of the direct thrombin antagonist bivalirudin given in combination with the glycoprotein IIb/IIIa antagonist eptifibatide. Am Heart J. 2002 Apr;143(4):585-93. Pubmed
  5. Carswell CI, Plosker GL: Bivalirudin: a review of its potential place in the management of acute coronary syndromes. Drugs. 2002;62(5):841-70. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Enzymes

1. Myeloperoxidase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Myeloperoxidase P05164 Details

References:

  1. Rudolph V, Rudolph TK, Schopfer FJ, Bonacci G, Lau D, Szocs K, Klinke A, Meinertz T, Freeman BA, Baldus S: Bivalirudin decreases NO bioavailability by vascular immobilization of myeloperoxidase. J Pharmacol Exp Ther. 2008 Nov;327(2):324-31. Epub 2008 Aug 13. Pubmed[

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Drug created on June 13, 2005 07:24 / Updated on September 13, 2013 10:48