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药品详细

Argatroban(阿加曲班)

化学结构式图
中文名
阿加曲班
英文名
Argatroban
分子式
C23H36N6O5S
化学名
(2R,4R)-1-[(2S)-5-[(diaminomethylidene)amino]-2-[(3R)-3-methyl-1,2,3,4-tetrahydroquinoline-8-sulfonamido]pentanoyl]-4-methylpiperidine-2-carboxylic acid
分子量
Average: 508.634
Monoisotopic: 508.246788982
CAS号
74863-84-6
ATC分类
B01A 抗血栓药
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Argatroban is a direct, selective thrombin inhibitor. The American College of Cardiologists (ACC) recommend using bivalirudin or argatroban in patients who have had, or at risk for, heparin induced thrombocytopenia (HIT) and are undergoing percutaneous coronary intervention. Argatroban is a non-heparin anticoagulant shown to both normalize platelet count in patients with HIT and prevent the formation of thrombi. Parental anticoagulants must be stopped and a baseline activated partial thromboplastin time must be obtained prior to administering argatroban.

生产厂家
  • Pfizer inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Di Nisio M, Middeldorp S, Buller HR: Direct thrombin inhibitors. N Engl J Med. 2005 Sep 8;353(10):1028-40. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Benzenesulfonamides
  • Phenylpropylamines
  • (Iso)quinolines and Derivatives
Substructures
  • Hydroxy Compounds
  • Acetates
  • Aliphatic and Aryl Amines
  • Amino Ketones
  • Sulfonyls
  • Benzene and Derivatives
  • Benzenesulfonamides
  • Carboxylic Acids and Derivatives
  • Heterocyclic compounds
  • Guanidines
  • Aromatic compounds
  • Carboxamidines
  • Carboxamides and Derivatives
  • Phenylpropylamines
  • (Iso)quinolines and Derivatives
  • Sulfonamides
  • Anilines
  • Piperidines
适应症
药理
Indication Argatroban is indicated for prevention and treatment of thrombosis caused by heparin induced thrombocytopenia (HIT). It is also indicated for use in patients with, or at risk for, HIT who are undergoing percutaneous coronary intervention.
Pharmacodynamics Argatroban is a synthetic direct thrombin inhibitor derived from L-arginine indicated as an anticoagulant for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia. Argatroban is a direct thrombin inhibitor that reversibly binds to the thrombin active site. Argatroban does not require the co-factor antithrombin III for antithrombotic activity. Argatroban exerts its anticoagulant effects by inhibiting thrombin-catalyzed or -induced reactions, including fibrin formation; activation of coagulation factors V, VIII, and XIII; protein C; and platelet aggregation. Argatroban is highly selective for thrombin with an inhibitory constant (Ki) of 0.04 µM. At therapeutic concentrations, Argatroban has little or no effect on related serine proteases (trypsin, factor Xa, plasmin, and kallikrein). Argatroban is capable of inhibiting the action of both free and clot-associated thrombin.
Mechanism of action Argatroban exerts its anticoagulant effects by inhibiting thrombin-catalyzed or -induced reactions, including fibrin formation; activation of coagulation factors V, VIII, and XIII; protein C; and platelet aggregation.
Absorption Bioavailability is 100% (intravenous).
Volume of distribution
  • 174 mL/kg
  • 12.18 L [70-kg adult]
Protein binding 54%
Metabolism
Liver via hydroxylation and aromatization of the 3-methyltetrahydroquinoline ring. Age and gender do not substantially affect the pharmacodynamic or pharmacokinetic profile of argatroban.
Route of elimination Argatroban is excreted primarily in the feces (65%), presumably through biliary secretion; 22% is eliminated via urine.
Half life 39 and 51 minutes
Clearance
  • 5.1 L/kg/hr [infusion doses up to 40 mcg/kg/min]
Toxicity Excessive bleeding
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00276 Argatroban Pathway SMP00276
理化性质
Properties
State solid
Experimental Properties
Property Value Source
logP 1 Not Available
Predicted Properties
Property Value Source
water solubility 2.21e-01 g/l ALOGPS
logP 0.19 ALOGPS
logP -0.97 ChemAxon
logS -3.4 ALOGPS
pKa (strongest acidic) 3.07 ChemAxon
pKa (strongest basic) 10.91 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 9 ChemAxon
hydrogen donor count 5 ChemAxon
polar surface area 180.21 ChemAxon
rotatable bond count 8 ChemAxon
refractivity 133.54 ChemAxon
polarizability 53.9 ChemAxon
药物相互作用
Drug Interaction
Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
Treprostinil The prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the anticoagulant, Argatroban. Monitor for increased bleeding during concomitant thearpy.
食物相互作用
  • Herbs and food with anticoagulant/antiplatelet activity. Major interactions may occur with danshen, dong quai, evening primrose oil, gingko, policosanol, willow bark

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