Antithrombin III human

Identification

Name
Antithrombin III human
Accession Number
DB11598
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Thrombolytic agents
Description

A plasma alpha 2 glycoprotein that accounts for the major antithrombin activity of normal plasma and also inhibits several other enzymes. It is a member of the serpin superfamily.

Protein chemical formula
Not Available
Protein average weight
Not Available
Sequences
Not Available
Synonyms
  • Antithrombin III
  • Antithrombin III (human)
  • Antithrombin III human plasma-derived
  • Antithrombin III, human
  • Antithrombin III,human
  • Antitrombina III
  • AT-III
  • Heparin cofactor B
External IDs
ORG 10849
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Thrombate IIIKit50 [iU]/1mLGRIFOLS USA, LLC1991-12-30Not applicableUs
Thrombate IIIPowder, for solution500 unitIntravenousGrifols Therapeutics Inc.Not applicableNot applicableCanada
Thrombate IIIKit50 [iU]/1mLGRIFOLS USA, LLC1991-12-30Not applicableUs
Thrombate IIIPowder, for solution1000 unitIntravenousGrifols Therapeutics Inc.1996-11-11Not applicableCanada
Thrombate IIIKit50 [iU]/1mLGRIFOLS USA, LLC1991-12-302017-06-22Us
Thrombate III Pws IV 1000iu/vialPowder, for solution1000 unitIntravenousMiles Inc. Pharmaceutical Division1995-12-311998-09-25Canada
Thrombate III Pws IV 500iu/vialPowder, for solution500 unitIntravenousMiles Inc. Pharmaceutical Division1995-12-311998-09-25Canada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Antithrombin III ImmunoAntithrombin III human (1650 unit) + Water (30 ml)Powder, for solutionIntravenousBaxter Ag1999-07-052011-10-07Canada
Antithrombin III NfAntithrombin III human (550 unit) + Water (10 ml)Kit; Powder, for solutionIntravenousBaxalta Canada Corporation1999-07-05Not applicableCanada
Antithrombin III NfAntithrombin III human (1100 unit) + Water (20 ml)Kit; Powder, for solutionIntravenousBaxalta Canada Corporation1999-07-05Not applicableCanada
International/Other Brands
Thrombate III
Categories
UNII
T0LTO7L82X
CAS number
9000-94-6

Pharmacology

Indication

Antithrombin III human is a human antithrombin (AT) indicated in patients with hereditary antithrombin deficiency for the treatment and prevention of thromboembolism and prevention of peri-operative and peri-partum thromboembolism

Associated Conditions
Pharmacodynamics

Hereditary AT deficiency causes an increased risk of venous thromboembolism (VTE). During high-risk situations such as surgery or trauma or for pregnant women, during the peri-partum period, the risk of development of VTEs as compared to the normal population in these situations is increased by a factor 10 to 50. In hereditary antithrombin deficient patients ATryn restores (normalize) plasma AT activity levels during peri-operative and peri-partum periods.

Mechanism of action

Antithrombin, an alpha2-glycoprotein of molecular weight 58,000, is normally present in human plasma at a concentration of approximately 12.5 mg/dL and is the major plasma inhibitor of thrombin. Inactivation of thrombin by AT occurs by formation of a covalent bond resulting in an inactive 1:1 stoichiometric complex between the two, involving an interaction of the active serine of thrombin and an arginine reactive site on AT. AT is also capable of inactivating other components of the coagulation cascade including factors IXa, Xa, XIa, and XIIa, as well as plasmin. The neutralization rate of serine proteases by AT proceeds slowly in the absence of heparin, but is greatly accelerated in the presence of heparin. As the therapeutic antithrombotic effect of heparin is mediated by AT, heparin in vivo is ineffective in the absence or near absence of AT. After administration, Antithrombin III human temporarily replaces the missing AT in patients with hereditary antithrombin deficiency.

TargetActionsOrganism
UAntithrombin-III
agonist
Human
Absorption

Therapeutic target plasma concentrations in patients with congenital antithrombin III deficiency range from 80–120% of values in healthy adults. At plasma concentrations ≤70% of normal, increased thrombin generation. Supraphysiologic plasma concentrations (e.g., 150–200% of normal) have increased bleeding risk in patients with sepsis and disseminated intravascular coagulation, not known whether supraphysiologic concentrations increase bleeding risk in patients with congenital antithrombin III deficiency.

Volume of distribution

Distributed into plasma (39%), extravascular space (49%), and vascular endothelial cells (11%).

Protein binding
Not Available
Metabolism

<5% metabolized to low molecular weight breakdown products.

Route of elimination

Complexes of antithrombin III with thrombin or other proteinases cleared principally by liver and excreted in urine.

Half life

2.5 - 3.8 hs

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(1,2,6,7-3H)TestosteroneThe therapeutic efficacy of Antithrombin III human can be increased when used in combination with (1,2,6,7-3H)Testosterone.
(R)-warfarinThe risk or severity of bleeding can be increased when Antithrombin III human is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Antithrombin III human is combined with (S)-Warfarin.
1-TestosteroneThe therapeutic efficacy of Antithrombin III human can be increased when used in combination with 1-Testosterone.
18-methyl-19-nortestosteroneThe therapeutic efficacy of Antithrombin III human can be increased when used in combination with 18-methyl-19-nortestosterone.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Antithrombin III human is combined with 4-hydroxycoumarin.
4-HydroxytestosteroneThe therapeutic efficacy of Antithrombin III human can be increased when used in combination with 4-Hydroxytestosterone.
5beta-dihydrotestosteroneThe therapeutic efficacy of Antithrombin III human can be increased when used in combination with 5beta-dihydrotestosterone.
AbacavirAbacavir may decrease the excretion rate of Antithrombin III human which could result in a higher serum level.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Antithrombin III human.
Food Interactions
Not Available

References

General References
  1. Cavenagh JD, Colvin BT: Guidelines for the management of thrombophilia. Department of Haematology, The Royal London Hospital, Whitechapel, London, UK. Postgrad Med J. 1996 Feb;72(844):87-94. [PubMed:8871458]
  2. Menache D, Grossman BJ, Jackson CM: Antithrombin III: physiology, deficiency, and replacement therapy. Transfusion. 1992 Jul-Aug;32(6):580-8. [PubMed:1502714]
  3. Aibiki M, Fukuoka N, Nishiyama T, Maekawa S, Shirakawa Y: Differences in antithrombin III activities by administration method in critical patients with disseminated intravascular coagulation: a pharmacokinetic study. Shock. 2007 Aug;28(2):141-7. [PubMed:17515857]
  4. Collen D, Schetz J, de Cock F, Holmer E, Verstraete M: Metabolism of antithrombin III (heparin cofactor) in man: effects of venous thrombosis and of heparin administration. Eur J Clin Invest. 1977 Feb;7(1):27-35. [PubMed:65284]
  5. FDA label [Link]
External Links
PubChem Substance
347911209
ATC Codes
B01AB02 — Antithrombin iii
AHFS Codes
  • 20:12.04.12 — Direct Thrombin Inhibitors

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1RecruitingTreatmentCardiopulmonary Bypass / Extracorporeal Membrane Oxygenation Complication1
1TerminatedTreatmentCongenital Heart Disease (CHD)1
2CompletedPreventionAcquired Antithrombin III Deficiency / Coronary Artery Bypass Graft Surgery Patients1
2CompletedTreatmentATIII Deficiency1
2CompletedTreatmentCardiopulmonary Bypass / Surgery, Cardiac1
2, 3Active Not RecruitingPreventionHereditary antithrombin III deficiency1
3CompletedTreatmentCardiopulmonary Bypass1
4Unknown StatusSupportive CareAcute Coronary Syndromes (ACS) / Aortic Valve Insufficiency / Aortic Valve Stenosis / Mitral Valve Insufficiency / Mitral Valve Stenosis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Powder, for solutionIntravenous
Kit; powder, for solutionIntravenous
Kit50 [iU]/1mL
Powder, for solutionIntravenous1000 unit
Powder, for solutionIntravenous500 unit
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Most important serine protease inhibitor in plasma that regulates the blood coagulation cascade. AT-III inhibits thrombin, matriptase-3/TMPRSS7, as well as factors IXa, Xa and XIa. Its inhibitory a...
Gene Name
SERPINC1
Uniprot ID
P01008
Uniprot Name
Antithrombin-III
Molecular Weight
52601.935 Da
References
  1. Menache D, Grossman BJ, Jackson CM: Antithrombin III: physiology, deficiency, and replacement therapy. Transfusion. 1992 Jul-Aug;32(6):580-8. [PubMed:1502714]

Drug created on May 20, 2016 14:36 / Updated on December 16, 2018 23:30