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Identification
NameTinzaparin
Accession NumberDB06822
Typesmall molecule
Groupsapproved
Description

Tinzaparin is a low molecular weight heparin (LMWH), produced by enzymatic depolymerization of unfractionated heparin from porcine intestinal mucosa. It is a heterogeneous mixture of with an average molecular weight between 5500 and 7500 daltons. Tinzaparin is composed of molecules with and without a special site for high affinity binding to antithrombin III (ATIII). This complex greatly accelerates the inhibition of factor Xa. It is an anticoagulant and considered an antithrombotic. Tinzaparin must be given either subcutaneously or parenterally. LMWHs are less effective at inactivating factor IIa due to their shorter length compared to unfractionated heparin.

Structure
Thumb
SynonymsNot Available
SaltsNot Available
Brand names
NameCompany
INNOHEPNot Available
Brand mixturesNot Available
Categories
CAS number9041-08-1
WeightNot Available
Chemical FormulaNot Available
InChI KeyNot Available
InChINot Available
IUPAC NameNot Available
SMILESNot Available
Mass SpecNot Available
Taxonomy
KingdomNot Available
SuperclassNot Available
ClassNot Available
SubclassNot Available
Direct parentNot Available
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationTinzaparin is used for the prevention of postoperative venous thromboembolism in patients undergoing orthopedic surgery and in patients undergoing general surgery who are at high risk of developing postoperative venous thromboembolism. It is also used for the treatment of deep vein thrombosis and/or pulmonary embolism. It is indicated for use in preventing clot formation in indwelling intravenous lines for hemodialysis.
PharmacodynamicsTinzaparin, like other LMWHs, have a higher anti-Xa activity than anti-IIa activity. The anti-Xa activity of tinzaparin is 2.0 +/- 0.5 times greater than its to anti-IIa activity. Heparin exhibits approximately equal inhibitory activity against Xa and IIa. Tinzaparin is an anticoagulant that blocks the formation of thrombi. Like all LMWHs, tinzaparin only causes activated partial thromboplastin time (aPTT) prolongation at higher doses and routine monitoring is not recommended. However, anti-factor Xa levels may be monitored in some conditions such as pregnancy and renal dysfunction. Its use should be avoided in patients with a creatinine clearance less than 20 mL/min. In these patients, unfractionated heparin should be used. Tinzaparin can be used in patients who have a creatinine clearance between 20-30 mL/min, giving it the highest safety threshold for use in renal failure patients compared to all the LMWHs.
Mechanism of actionTinzaparin binds to the plasma protein antithrombin III, forming a complex with then accelerates the inhibition of factor Xa. Its affinity for factor Xa is 2-4 times greater than that of unbound ATIII. The inactivation of factor Xa in turn will exponentially generation of thrombin (factor IIa) molecules, which is needed to activate fibrinogen to fibrin. The coagulation cascade is inhibited because fibrin cannot be formed in the presence of tinzaparin. Like all LMWH, it cannot be given intramuscularly due to increased risk of hematoma.
AbsorptionSubcutaneous injection - about 90% when measured as anti-Xa activity versus 67% for anti-IIa activity.
Volume of distribution

Anti-Xa activity is 4 L. Anti-IIa activity is 10.9 L

Protein bindingLow protein binding compared to unfractionated heparin.
Metabolism

Sulfation and polymerization occurs in the liver.

Route of eliminationLinear elimination through kidneys
Half lifeAnti-Xa activity is 82 minutes. Anti-IIa activity is 71 minutes.
Clearance

Clearance is dose-dependant. The clearance of tinzaparin based on anti-Xa activity ranged from 1.14 to 2.04 L/hr

ToxicityOsteoporosis with increasing duration of use, bleeding, alopecia, heparin induced thrombocytopenia (HIT). All of these adverse drug reactions occur less with LMWH compared to unfractionated heparin. Tinzaparin showed no toxic effects at doses up to 5 mg/kg in mice, rats, or dogs in standard acute, subacute, and chronic toxicity studies.
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption Not Available Not Available
Blood Brain Barrier Not Available Not Available
Caco-2 permeable Not Available Not Available
P-glycoprotein substrate Not Available Not Available
P-glycoprotein inhibitor I Not Available Not Available
P-glycoprotein inhibitor II Not Available Not Available
Renal organic cation transporter Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 1A2 substrate Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 2C19 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 inhibitory promiscuity Not Available Not Available
Ames test Not Available Not Available
Carcinogenicity Not Available Not Available
Biodegradation Not Available Not Available
Rat acute toxicity Not Available Not applicable
hERG inhibition (predictor I) Not Available Not Available
hERG inhibition (predictor II) Not Available Not Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
InjectionParenteral10 000 IU/mL
InjectionParenteral20 000 IU/mL
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Predicted PropertiesNot Available
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Friedel HA, Balfour JA: Tinzaparin. A review of its pharmacology and clinical potential in the prevention and treatment of thromboembolic disorders. Drugs. 1994 Oct;48(4):638-60. Pubmed
  2. Simonneau G, Sors H, Charbonnier B, Page Y, Laaban JP, Azarian R, Laurent M, Hirsch JL, Ferrari E, Bosson JL, Mottier D, Beau B: A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. The THESEE Study Group. Tinzaparine ou Heparine Standard: Evaluations dans l’Embolie Pulmonaire. N Engl J Med. 1997 Sep 4;337(10):663-9. Pubmed
  3. Planes A, Samama MM, Lensing AW, Buller HR, Barre J, Vochelle N, Beau B: Prevention of deep vein thrombosis after hip replacement—comparison between two low-molecular heparins, tinzaparin and enoxaparin. Thromb Haemost. 1999 Jan;81(1):22-5. Pubmed
  4. Cheer SM, Dunn CJ, Foster R: Tinzaparin sodium: a review of its pharmacology and clinical use in the prophylaxis and treatment of thromboembolic disease. Drugs. 2004;64(13):1479-502. Pubmed
  5. Hoy SM, Scott LJ, Plosker GL: Tinzaparin sodium: a review of its use in the prevention and treatment of deep vein thrombosis and pulmonary embolism, and in the prevention of clotting in the extracorporeal circuit during haemodialysis. Drugs. 2010 Jul 9;70(10):1319-47. doi: 10.2165/11203710-000000000-00000. Pubmed
  6. Hedner U: Development of tinzaparin: a heparinase-digested low-molecular-weight heparin. Semin Thromb Hemost. 2000;26 Suppl 1:23-9. Pubmed
  7. Pautas E, Siguret V, d’Urso M, Laurent M, Gaussem P, Fevrier M, Durand-Gasselin B: [Monitoring of tinzaparin in a ten day treatment dose in elderly patients]. Rev Med Interne. 2001 Feb;22(2):120-6. Pubmed
  8. Pineo GF, Hull RD: Tinzaparin in the treatment of venous thromboembolism. Expert Opin Pharmacother. 2003 Dec;4(12):2355-62. Pubmed
  9. Fossler MJ, Barrett JS, Hainer JW, Riddle JG, Ostergaard P, van der Elst E, Sprogel P: Pharmacodynamics of intravenous and subcutaneous tinzaparin and heparin in healthy volunteers. Am J Health Syst Pharm. 2001 Sep 1;58(17):1614-21. Pubmed
  10. Cambus JP, Saivin S, Heilmann JJ, Caplain H, Boneu B, Houin G: The pharmacodynamics of tinzaparin in healthy volunteers. Br J Haematol. 2002 Mar;116(3):649-52. Pubmed
External Links
ResourceLink
ATC CodesB01AB10
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
Drotrecogin alfaLow molecular weight heparins (LMWHs) such as tinzaparin may enhance the adverse/toxic effects of drotrecogin alfa. Bleeding may occur. The potential benefits of drotrecogin alfa should be weighed against the increased risk of bleeding in patients on therapeutic doses of LMWHs.
Food Interactions
  • Herbs with anticoagulant/antiplatelet properties (ginger, gingko, garlic) may increase the risk of bleeding.

Targets

1. Antithrombin-III

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Antithrombin-III P01008 Details

References:

  1. Bisio A, Vecchietti D, Citterio L, Guerrini M, Raman R, Bertini S, Eisele G, Naggi A, Sasisekharan R, Torri G: Structural features of low-molecular-weight heparins affecting their affinity to antithrombin. Thromb Haemost. 2009 Nov;102(5):865-73. Pubmed
  2. Florian-Kujawski M, Hoppensteadt D, Maddineni J, Ziegler H, Fareed J: Differential regulation of thrombin activatable fibrinolytic inhibitor by low molecular weight heparins. Pharmacologic implications. Int Angiol. 2004 Dec;23(4):346-54. Pubmed
  3. Morris TA, Jacobson A, Marsh JJ, Lane JR: Pharmacokinetics of UH and LMWH are similar with respect to antithrombin activity. Thromb Res. 2005;115(1-2):45-51. Pubmed

2. Integrin alpha-4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Integrin alpha-4 P13612 Details

References:

  1. Schlesinger M, Simonis D, Schmitz P, Fritzsche J, Bendas G: Binding between heparin and the integrin VLA-4. Thromb Haemost. 2009 Nov;102(5):816-22. Pubmed

3. Stromal cell-derived factor 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Stromal cell-derived factor 1 P48061 Details

References:

  1. Koo CY, Sen YP, Bay BH, Yip GW: Targeting heparan sulfate proteoglycans in breast cancer treatment. Recent Pat Anticancer Drug Discov. 2008 Nov;3(3):151-8. Pubmed

Enzymes

1. A disintegrin and metalloproteinase with thrombospondin motifs 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
A disintegrin and metalloproteinase with thrombospondin motifs 4 O75173 Details

References:

  1. Mousa SA: Effect of low molecular weight heparin and different heparin molecular weight fractions on the activity of the matrix-degrading enzyme aggrecanase: structure-function relationship. J Cell Biochem. 2005 May 1;95(1):95-8. Pubmed

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Drug created on September 14, 2010 10:21 / Updated on January 18, 2012 15:53