| Primary information |
|---|
| ThPP ID | Th1006 |
| Therapeutic Peptide/Protein Name | Bivalirudin |
| Sequence | FPRPGGGGNGDFEEIPEEYL view full sequnce in fasta |
| Functional Classification | Ia |
| Molecular Weight | 2180.2853 |
| Chemical Formula | C98H138N24O33 |
| Isoelectric Point | 3.91 |
| Hydrophobicity | -0.985 |
| Melting Point (℃) | N.A. |
| Half Life | Normal renal function: 0.42 hours (in normal conditions) |
| Description | Bivalirudin is a synthetic 20 residue peptide which acts as a thrombin inhibitor. Once bound to the active site of the inhibitor, thrombin cannot activate fibrinogen into fibrin which is a crucial step in the formation of thrombus. As it can cause blood stagnation, it is important to monitor changes in hematocrit, activated partial thromboplastin time, international normalized ratio and blood pressure. It is administered intravenously. |
| Indication/Disease | For 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. |
| Pharmacodynamics | Bivalirudin directly and reversibly inhibits thrombin by specifically binding to both the catalytic site and the anion-binding exosite of circulating and clot-bound thrombin. The action of bivalirudin is reversible as thrombin will slowly cleave the thrombin-bivalirudin bond which recovers the active site of thrombin. |
| Mechanism of Action | Inhibits the action of thrombin by binding to both its catalytic site and to its anion-binding exosite. Thrombin, a serine proteinase that plays a central role in the thrombotic process, acts to cleave fibrinogen into fibrin monomers and 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. |
| Toxicity | Based 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. |
| Metabolism | 80% proteolytic cleavage |
| Absorption | 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 |
| Clearance | 3.4 mL/min/kg [Normal renal function] |
| Categories | Antithrombins |
| Patents Number | US7582727 |
| Date of Issue | 27/01/09 |
| Date of Expiry | 27/01/29 |
| Drug Interaction | Deferasirox, Anticoagulants 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. |
| Target | Prothrombin |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Angiomax |
| Company | Medicines Co or MDCO |
| Brand Discription | Angiomax is a specific and reversible thrombin inhibitor. The active substance is a synthetic, 20 amino acid peptide with a molecular weight of 2180 daltons (anhydrous free base peptide). |
| Prescribed for | It is used for thinning the blood in patients with unstable angina who are undergoing percutaneous transluminal coronary angioplasty (PTCA) and in patients undergoing percutaneous coronary intervention (PCI). |
| Chemical Name | D-phenylalanyl-L-prolyl-L-arginyl-L-prolyl-glycylglycyl-glycyl-glycyl-L-asparagyl-glycyl-L-aspartyl-L-phenylalanyl-L-glutamyl-L-glutamyl-L-isoleucyl-L-prolyl-L-glutamyl-L-glutamyl-L-tyrosyl-L-leucine trifluoroacetate (salt) hydrate |
| Formulation | Each vial contains 250 mg bivalirudin, 125 mg mannitol, and sodium hydroxide to adjust the pH to 5-6 (equivalent of approximately 12.5 mg sodium). When reconstituted with Sterile Water for Injection, the product yields a clear to opalescent, colorless to |
| Physcial Appearnce | Supplied in single-use vials as a white lyophilized cake |
| Route of Administration | Intravenous infusion |
| Recommended Dosage | Intravenous (IV) bolus dose of 0.75Â mg/kg, followed by an infusion of 1.75Â mg/kg/h for the duration of the PCI/PTCA procedure. |
| Contraindication | Allergic and have major active bleeding |
| Side Effects | Anxiety; back, stomach, or pelvic pain; headache; nausea; nervousness; pain at the injection site; trouble sleeping; upset stomach; vomiting. And severe side effect may include Severe allergic reactions (rash; hives; itching; difficulty breathing. |
| Useful Link | http://reference.medscape.com/drug/angiomax-angiox-bivalirudin-342137 |
| PubMed ID | 17381384, 16553503, 16466327, 12851152, 11156732 |
| 3-D Structure | Th1006 (View) or (Download) |