Absorption, Distribution and Excretion
Following intravenous injection, bivalirudin exhibits linear pharmacokinetics. After a bolus injection of 1 mg/kg, continuous intravenous infusion at a rate of 2.5 mg/kg/hr over 4 hours resulted in a mean steady-state concentration of 12.3 ± 1.7 mcg/mL. Bivalirudin is primarily cleared from plasma via renal mechanisms (20%) and proteolytic activity. 0.2 L/kg
3.4 mL/min/kg [Normal Renal Function]
3.4 mL/min/kg [Mild Renal Insufficiency]
2.7 mL/min/kg [Moderate Renal Insufficiency]
2.8 mL/min/kg [Severe Renal Insufficiency]
1 mL/min/kg [Dialysis-Dependent Patient]

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Metabolism/Metabolites
80% Protein Hydrolysis

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Biological Half-Life
Normal Renal Function: 25 minutes (under normal conditions)
Cretin clearance 10-29 mL/min: 57 minutes
Dialysis-Dependent Patient: 3.5 hours

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
There is currently no information regarding the use of bivalirudin during lactation. Since this drug is absorbed orally, alternative medications are recommended.
◉ Effects on Breastfed Infants
As of the revision date, no relevant published information was found.
◉ Effects on Lactation and Breast Milk
As of the revision date, no relevant published information was found.

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Protein Binding
Except for thrombin and erythrocytes, bivalirudin does not bind to plasma proteins.

[1]. Ciborowski M, Tomasiak M. The in vitro effect of eptifibatide, a glycoprotein IIb/IIIa antagonist, on various responses of porcine blood platelets. Acta Pol Pharm. 2009 May-Jun;66(3):235-42.

[2]. Xu Y, Wu W, Wang L, Differential profiles of thrombin inhibitors (heparin, hirudin, bivalirudin, and dabigatran) in the thrombin generation assay and thromboelastography in vitro. Blood Coagul Fibrinolysis. 2013 Apr;24(3):332-8.

[3]. Rudolph V, Rudolph TK, Schopfer FJ, Bivalirudin decreases NO bioavailability by vascular immobilization of myeloperoxidase. J Pharmacol Exp Ther. 2008 Nov;327(2):324-31.

[4]. Zhang R, Huang Y, Zhang M, Bivalirudin Utilization in Rats Undergoing Cardiopulmonary Bypass: Preventing the Increase of Antiheparin/Platelet Factor 4 Antibody in Perioperative Period. Clin Appl Thromb Hemost. 2012 Aug 21. [Epub ahead of print].

[5]. Gleason TG, Chengelis CP, Jackson CB, A 24-hour continuous infusion study of bivalirudin in the rat. Int J Toxicol. 2003 May-Jun;22(3):195-206.

Bivalirudin is a synthetic peptide composed of 20 amino acids, with the following amino acid sequence: D-Phe, Pro, Arg, Pro, Gly, Gly, Gly, Gly, Asn, Gly, Asp, Phe, Glu, Glu, Ile, Pro, Glu, Glu, Tyr, and Leu. It is a homologue of hirudin (a natural drug found in the saliva of medicinal leeches) and is a specific and reversible thrombin inhibitor used as an anticoagulant. It is both an anticoagulant and an EC 3.4.21.5 (thrombin) inhibitor. Bivalirudin is a synthetic peptide (thrombin inhibitor) composed of 20 amino acid residues that reversibly inhibits thrombin. Once bound to its active site, thrombin cannot activate fibrinogen to form fibrin, a key step in thrombosis. It is administered intravenously. Because bivalirudin can cause blood stasis, monitoring changes in hematocrit, activated partial thromboplastin time, international normalized ratio, and blood pressure is crucial. Bivalirudin is a synthetic peptide composed of 20 amino acids with thrombin-specific anticoagulant properties. Bivalirudin reversibly binds to the catalytic and anion-binding sites of thrombin (including free thrombin and thromboconjugated thrombin), thereby preventing the formation and activation of fibrin, factor XIIIa, and other coagulation factors. This drug is primarily used during coronary angioplasty and is often used in combination with aspirin for patients with unstable angina. Bivalirudin trifluoroacetate is the trifluoroacetate form of bivalirudin, a synthetic peptide composed of 20 amino acids with thrombin-specific anticoagulant activity. After intravenous injection, bivalirudin reversibly binds to the catalytic and anion-binding sites of thrombin (including free thrombin and thromboconjugated thrombin), thereby preventing the formation and activation of fibrin, factor XIIIa, and other coagulation factors. Bivalirudin is primarily used during coronary angioplasty and is often used in combination with aspirin for patients with unstable angina. Drug Indications For the treatment of heparin-induced thrombocytopenia and prevention of thrombosis. Bivalirudin is indicated for patients undergoing percutaneous coronary intervention (PCI) and for patients with moderate to high-risk acute coronary syndrome due to unstable angina or non-ST-segment elevation myocardial infarction who are scheduled for PCI. FDA Label Angiox is indicated for adult patients undergoing percutaneous coronary intervention (PCI), including patients with ST-segment elevation myocardial infarction (STEMI) undergoing emergency PCI. Angiox is also indicated for adult patients with unstable angina/non-ST-segment elevation myocardial infarction (UA/NSTEMI) who are scheduled for emergency or early intervention. Angiox should be used in combination with aspirin and clopidogrel. Treatment of Atherosclerosis and Thrombosis Mechanism of Action Inhibits thrombin activity by binding to the catalytic and anion-binding sites of thrombin. Thrombin is a serine protease that plays a central role in thrombus formation. It cleaves fibrinogen into fibrin monomers and activates factor XIII to factor XIIIa, enabling fibrin to form a covalently cross-linked framework, thereby stabilizing the thrombus. Thrombin also activates factors V and VIII, promoting further thrombin production and activating platelets, stimulating their aggregation and particle release.

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Pharmacodynamics
Bivalirudin exerts its inhibitory effect on thrombin by directly and specifically binding to the catalytic and anion-binding sites of circulating and thrombus-binding thrombin. The effect of bivalirudin is reversible because thrombin slowly cleaves the thrombin-bivalirudin bond, thereby restoring the active site of thrombin.

C98H138N24O33

2180.285343647

2178.985

1191386-55-6

Bivalirudin;128270-60-0

16129704

White to off-white solid powder

1.5±0.1 g/cm3

1.675

-2.24

28

35

67

155

4950

16

CC[C@H](C)[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)N)NC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)[C@@H]4CCCN4C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]5CCCN5C(=O)[C@@H](CC6=CC=CC=C6)N

OIRCOABEOLEUMC-GEJPAHFPSA-N

InChI=1S/C98H138N24O33/c1-5-52(4)82(96(153)122-39-15-23-70(122)92(149)114-60(30-34-79(134)135)85(142)111-59(29-33-78(132)133)86(143)116-64(43-55-24-26-56(123)27-25-55)89(146)118-67(97(154)155)40-51(2)3)119-87(144)61(31-35-80(136)137)112-84(141)58(28-32-77(130)131)113-88(145)63(42-54-18-10-7-11-19-54)117-90(147)66(45-81(138)139)110-76(129)50-107-83(140)65(44-71(100)124)109-75(128)49-106-73(126)47-104-72(125)46-105-74(127)48-108-91(148)68-21-13-38-121(68)95(152)62(20-12-36-103-98(101)102)115-93(150)69-22-14-37-120(69)94(151)57(99)41-53-16-8-6-9-17-53/h6-11,16-19,24-27,51-52,57-70,82,123H,5,12-15,20-23,28-50,99H2,1-4H3,(H2,100,124)(H,104,125)(H,105,127)(H,106,126)(H,107,140)(H,108,148)(H,109,128)(H,110,129)(H,111,142)(H,112,141)(H,113,145)(H,114,149)(H,115,150)(H,116,143)(H,117,147)(H,118,146)(H,119,144)(H,130,131)(H,132,133)(H,134,135)(H,136,137)(H,138,139)(H,154,155)(H4,101,102,103)/t52-,57+,58-,59-,60-,61-,62-,63-,64-,65-,66-,67-,68-,69-,70-,82-/m0/s1

(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[2-[[2-[[2-[[2-[[(2S)-1-[(2S)-2-[[(2S)-1-[(2R)-2-amino-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]acetyl]amino]acetyl]amino]acetyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-carboxypropanoyl]amino]-3-phenylpropanoyl]amino]-4-carboxybutanoyl]amino]-4-carboxybutanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-4-carboxybutanoyl]amino]-4-carboxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ≥ 50 mg/mL (~21.79 mM)
DMSO : ≥ 31 mg/mL (~13.51 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (1.09 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (1.09 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (1.09 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 50 mg/mL (21.79 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)