DT-Web

DB00006 - Bivalirudin


Identification
Name Bivalirudin
Accession Number DB00006 (BIOD00076, BTD00076)
Type biotech
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.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 2180.2853
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication 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.
Mechanism of action Inhibits 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.
Absorption Following 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.
Protein binding Other than thrombin and red blood cells, bivalirudin does not bind to plasma proteins.
Biotransformation 80% proteolytic cleavage
Route of elimination Bivalirudin is cleared from plasma by a combination of renal mechanisms (20%) and proteolytic cleavage.
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.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of 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.
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.
Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
Rivaroxaban Anticoagulants 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.
Treprostinil The 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


Prothrombin
Name Prothrombin
Gene Name F2
Pharmacological action yes
Actions inhibitor
References
  • Scatena R: Bivalirudin: a new generation antithrombotic drug. Expert Opin Investig Drugs. 2000 May;9(5):1119-27. - Pubmed
  • Bates ER: Bivalirudin for percutaneous coronary intervention and in acute coronary syndromes. Curr Cardiol Rep. 2001 Sep;3(5):348-54. - Pubmed
  • Gladwell TD: Bivalirudin: a direct thrombin inhibitor. Clin Ther. 2002 Jan;24(1):38-58. - Pubmed
  • 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
  • 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
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 1.5875

Enzymes


Myeloperoxidase
Name Myeloperoxidase
Gene Name MPO
Actions inhibitor
References
  • 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
DTHybrid score 0.3106

Predictions


Id Partner name Gene Name Score
3176 Trypsin-1 PRSS1 0.1044
239 Coagulation factor X F10 0.0561
290 Prostaglandin G/H synthase 2 PTGS2 0.0391
1074 Urokinase-type plasminogen activator PLAU 0.0362
1736 Somatostatin SST 0.0311
4186 Neuropeptide Y receptor type 2 NPY2R 0.0311
20 Prostaglandin G/H synthase 1 PTGS1 0.0268
309 Antithrombin-III SERPINC1 0.0251
3997 Cytochrome P450 24A1, mitochondrial CYP24A1 0.0239
563 Thyroid peroxidase TPO 0.0238
153 Dopamine beta-hydroxylase DBH 0.0238
723 Cytosolic phospholipase A2 PLA2G4A 0.0232
275 Arachidonate 5-lipoxygenase ALOX5 0.0215
503 Somatostatin receptor type 1 SSTR1 0.0214
3866 Serum amyloid A protein SAA1 0.0209
1932 Apolipoprotein E APOE 0.0208
1200 AMBP protein AMBP 0.0208
61 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase folK 0.0201
2644 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase folK 0.0201
2710 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase folK 0.0201
3872 Somatostatin receptor type 5 SSTR5 0.02
6008 Somatostatin receptor type 2 SSTR2 0.02
6020 Aldehyde oxidase AOX1 0.0196
1974 Oligopeptide transporter, kidney isoform SLC15A2 0.019
856 Vitamin D3 receptor VDR 0.0189
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0183
4757 Cytochrome P450 2C9 CYP2C9 0.018
369 Coagulation factor VII F7 0.0173
3119 Fimbrial protein pilE1 0.0168
115 Penicillin-binding protein 2 mrdA 0.016
6069 Penicillin-binding protein 2 mrdA 0.016
6118 Penicillin-binding protein 2 penA 0.016
6187 Penicillin-binding protein 2 pbpA 0.016
6686 Penicillin-binding protein 2 pbp2 0.016
6939 Penicillin-binding protein 2 mrdA 0.016
7163 Penicillin-binding protein 2 pbpA 0.016
867 Penicillin-binding protein 3 pbpC 0.016
6119 Penicillin-binding protein 3 pbp3 0.016
7154 Penicillin-binding protein 3 pbp3 0.016
7157 Penicillin-binding protein 3 LMHCC_2184 0.016
7162 Penicillin-binding protein 3 pbpB 0.016
7172 Penicillin-binding protein 3 pbp3 0.016
6012 Tryptophan 2,3-dioxygenase TDO2 0.0155
4200 Cytochrome P450 1A2 CYP1A2 0.0151
6165 Copper-transporting ATPase 1 ATP7A 0.0132
6163 Copper-transporting ATPase 2 ATP7B 0.0132
633 Penicillin-binding proteins 1A/1B pbpA 0.0132
6146 High affinity copper uptake protein 1 SLC31A1 0.0125
6564 Prephenate dehydrogenase tyrA 0.0122
6240 Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 PIN1 0.0122
4152 Superoxide dismutase [Cu-Zn] SOD1 0.0121
6270 Group IIE secretory phospholipase A2 PLA2G2E 0.0121
908 Glutathione S-transferase theta-1 GSTT1 0.0119
2038 Inhibitor of nuclear factor kappa-B kinase subunit beta IKBKB 0.0119
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.011
2157 NAD(P)H dehydrogenase [quinone] 1 NQO1 0.0109
3947 Xanthine dehydrogenase/oxidase XDH 0.0107
896 Glutathione S-transferase Mu 1 GSTM1 0.0105
118 Organic cation/carnitine transporter 2 SLC22A5 0.0103
2331 HTH-type transcriptional regulator qacR qacR 0.01
6461 HTH-type transcriptional regulator qacR qacR 0.01
6161 Probable low affinity copper uptake protein 2 SLC31A2 0.0098
6828 TetR family transcriptional repressor LfrR lfrR 0.0095
904 Glutathione S-transferase P GSTP1 0.0094
256 Tyrosyl-tRNA synthetase, cytoplasmic YARS 0.0093
3384 Macrophage migration inhibitory factor MIF 0.009
6024 Cytochrome P450 1A1 CYP1A1 0.0084
6013 Cytochrome P450 2E1 CYP2E1 0.0084
19 Coagulation factor VIII F8 0.0083
243 Ribosyldihydronicotinamide dehydrogenase [quinone] NQO2 0.0082
3830 Calreticulin CALR 0.0081
713 Sodium-dependent dopamine transporter SLC6A3 0.008
3941 Amine oxidase [flavin-containing] A MAOA 0.008
238 Peroxisome proliferator-activated receptor gamma PPARG 0.008
3939 Amine oxidase [flavin-containing] B MAOB 0.008
798 Osteocalcin BGLAP 0.008
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0076
3831 Low-density lipoprotein receptor-related protein 1 LRP1 0.0075
1729 Solute carrier family 22 member 6 SLC22A6 0.0075
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0075
4512 Cytochrome P450 3A4 CYP3A4 0.0072
3851 Serine protease hepsin HPN 0.0071
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0071
6016 Cytochrome P450 2C19 CYP2C19 0.007
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0069
4604 Liver carboxylesterase 1 CES1 0.0068
109 Mitochondrial carnitine/acylcarnitine carrier protein CACL SLC25A29 0.0067
636 Mitochondrial carnitine/acylcarnitine carrier protein SLC25A20 0.0067
3601 Dihydropteroate synthase 1 folP1 0.0065
3807 Dihydropteroate synthase 1 folP1 0.0065
3808 Dihydropteroate synthase 2 folP2 0.0065
448 Vitamin K-dependent gamma-carboxylase GGCX 0.0064
122 P2Y purinoceptor 12 P2RY12 0.0062
6036 Eosinophil peroxidase EPX 0.0059
6168 Solute carrier family 22 member 16 SLC22A16 0.0058
4118 Cytochrome P450 3A5 CYP3A5 0.0058
200 Carnitine O-palmitoyltransferase 2, mitochondrial CPT2 0.0058
451 Carnitine O-palmitoyltransferase I, liver isoform CPT1A 0.0058
412 Peroxisomal carnitine O-octanoyltransferase CROT 0.0057
551 Carnitine O-acetyltransferase CRAT 0.0057
6034 Hydroxyindole O-methyltransferase ASMT 0.0055
6035 Nuclear receptor ROR-beta RORB 0.0055
4924 Cytochrome P450 2C8 CYP2C8 0.0054
1898 Cytochrome P450 1B1 CYP1B1 0.0053
6142 Solute carrier family 22 member 8 SLC22A8 0.0051
6030 Cytochrome P450 2B6 CYP2B6 0.0049
765 Indoleamine 2,3-dioxygenase IDO1 0.0047
4165 P2Y purinoceptor 2 P2RY2 0.0047
6102 Arylamine N-acetyltransferase 2 NAT2 0.0045
362 Melatonin receptor type 1B MTNR1B 0.0045
571 Melatonin receptor type 1A MTNR1A 0.0045
6144 Solute carrier family 22 member 2 SLC22A2 0.0042
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0041
400 Coagulation factor IX F9 0.0039
5461 Coagulation factor IX F9 0.0039
1547 Coagulation factor XI F11 0.0039
2654 Complement control protein C3L 0.0037
1959 Platelet factor 4 PF4 0.0035
3865 Serpin B6 SERPINB6 0.0035
1986 Ceruloplasmin CP 0.0035
833 Organic cation/carnitine transporter 1 SLC22A4 0.0035
1245 Vitamin K-dependent protein S PROS1 0.0035
430 Follicle-stimulating hormone receptor FSHR 0.0034
5766 NAD-dependent deacetylase sirtuin-5 SIRT5 0.0034
422 Vitamin K-dependent protein C PROC 0.0033
6106 Cytochrome P450 2C18 CYP2C18 0.0033
3842 Multiple coagulation factor deficiency protein 2 MCFD2 0.0033
3841 ERGIC-53 protein LMAN1 0.0033
3840 Asialoglycoprotein receptor 2 ASGR2 0.0033
1847 78 kDa glucose-regulated protein HSPA5 0.0033
1635 von Willebrand factor VWF 0.0033
5455 Arylsulfatase A ARSA 0.0032
3833 Plasma serine protease inhibitor SERPINA5 0.0031
2072 Endothelial protein C receptor PROCR 0.0031
46 Coagulation factor V F5 0.0031
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.003
1588 Multidrug resistance protein 1 ABCB1 0.003
465 Calmodulin CALM1 0.0029
814 Ryanodine receptor 1 RYR1 0.0029
1516 Calnexin CANX 0.0028
4119 Cytochrome P450 2D6 CYP2D6 0.0028
6147 Solute carrier family 22 member 3 SLC22A3 0.0027
2981 Phospholipase A2, membrane associated PLA2G2A 0.0026
2021 Thrombomodulin THBD 0.0026
468 Cytochrome P450 4A11 CYP4A11 0.0026
6137 Multidrug resistance-associated protein 6 ABCC6 0.0026
3811 Cytochrome P450 19A1 CYP19A1 0.0026
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0025
6107 Cytochrome P450 3A7 CYP3A7 0.0024
136 Estrogen receptor ESR1 0.0024
6136 Multidrug resistance-associated protein 5 ABCC5 0.0024
3839 Phytanoyl-CoA dioxygenase, peroxisomal PHYH 0.0023
267 Plasminogen activator inhibitor 1 SERPINE1 0.0023
6145 Solute carrier family 22 member 1 SLC22A1 0.0023
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0021
3923 Cholinesterase BCHE 0.0018
604 Vitamin K-dependent protein Z PROZ 0.0014
4081 Vitamin K epoxide reductase complex subunit 1-like protein 1 VKORC1L1 0.0014
787 Vitamin K epoxide reductase complex subunit 1 VKORC1 0.001
3917 Methylenetetrahydrofolate reductase MTHFR 0.0009
5718 Cytochrome P450 2A6 CYP2A6 0.0006
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