| 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 | Creatinine clearance 10-29mL/min: 0.95 hours |
| 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 [mild renal function] |
| Categories | Antithrombins |
| Patents Number | US5196404 |
| Date of Issue | 23/05/93 |
| Date of Expiry | 23/05/10 |
| Drug Interaction | Gemcitabine, Gemcitabine 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 |
| Target | N.A. |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Angiox |
| Company | The Medicines Company UK Ltd |
| Brand Discription | N.A. |
| Prescribed for | Used as an anticoagulant in adult patients undergoing percutaneous coronary intervention (PCI), including patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. Angiox is also indicated for the treatment of adult patients |
| Chemical Name | N.A. |
| Formulation | Each vial contains 250 mg bivalirudin. |
| Physcial Appearnce | Powder for concentrated solution |
| Route of Administration | Injection |
| Recommended Dosage | 0.75 mg/kg IV bolus, initially, followed by continuous infusion at rate of 1.75 mg/kg/hr for duration of procedure |
| Contraindication | Hypersensitivity, active bleeding or increased risk of bleeding because of haemostasis disorder or irreversible coagulation disorder, uncontrolled hypertension, subacute bacterial endocarditis, severe renal impairment and in dialysis dependent pateints, |
| Side Effects | N.A. |
| Useful Link | http://www.rxlist.com/angiomax-drug.htm |
| PubMed ID | 17381384, 16553503, 16466327, 12851152, 11156732 |
| 3-D Structure | Th1006 (View) or (Download) |