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Identification
Name Nadroparin
Accession Number DB08813
Type small molecule
Groups approved
Description

Nadroparin is a low molecular weight heparin (LMWH) which, when bound to antithrombin III (ATIII), accelerates the inactivation of factor II and factor Xa. Nadroparin halts the coagulation pathway by inhibiting the activation of thrombin (factor IIa) by factor Xa. The amplification of the fibrin clotting cascade is stopped once factors Xa and IIa are inactivated. It is derived from porcine sources and has a mean molecular size of 5000 daltons. Low molecular weight heparins are less effective at inactivating factor IIa due to their shorter length compared to unfractionated heparin.
Structure Thumb
Synonyms Not Available
Salts Not Available
Brand names Not Available
Brand mixtures Not Available
Categories
  • Anticoagulants
  • Antithrombotics
CAS number 9041-08-1
Weight Not Available
Chemical Formula Not Available
InChI Key Not Available
InChI Not Available
IUPAC Name Not Available
SMILES Not Available
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication Nadroparin is used for prophylaxis of thromboembolic disorders and general surgery in orthopedic surgery, treatment of deep vein thrombosis, prevention of clotting during hemodialysis and treatment of unstable angina and non-Q wave myocardial infarction
Pharmacodynamics Nadroparin is a low molecular weight heparin that is composed of a heterogeneous mixture of sulfated polysaccaride glycosaminoglycan chains. Th mean molecular weight is approximately 4300 daltons. The ratio of anti-Xa activity to anti-IIa is 3.5:1 whereas it is about 1:1 for heparin. Its use should be avoided in patients with a creatinine clearance less than 40mL/min. In these patients, unfractionated heparin should only be used. As for monitoring, active partial thromboplastin time (aPTT) will only increase at high doses of low molecular weight heparins (LMWH). Therefore, monitoring aPTT is not recommended. However, anti-Xa activity can be measured to monitor the efficacy of the LMWH.
Mechanism of action The mechanism of action for nadroparin is similar to all other LMWHs. Like all LMWHs, nadroparin has a pentasaccharide sequence which binds to ATIII, which potentiates the action of ATIII. This complex greatly accelerates the inactivation of factor Xa and factor IIa. As a result, the coagulation cascade is inhibited.
Absorption Absorption is linear. The bioavailability of nadroparin after subcutaneous administration is about 89%.
Volume of distribution

3.59L
Protein binding Much lower compared to heparin, which has over 90% protein bound.
Metabolism Nadroparin is metabolized in the liver.
Route of elimination Nadroparin is eliminated via the kidneys through non-saturable mechanisms.
Half life In healthy patients, the half life is between 3.5hrs to 11.2hrs following subcutaneous administration.
Clearance

The clearance of nadroparin is 21.4 +/- 7.0mL/min
Toxicity Osteopenia with extended use, skin necrosis, thrombocytosis, severe immunologically-mediated thrombocytopenia, eosinophilia (rare), calcinosis rarely occurs at the injection site, severe bleeding, transient elevation of liver transaminases.
Affected organisms Not Available
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms
Form Route Strength
Injection, solution Subcutaneous 11 400IU/0.6mL
Injection, solution Subcutaneous 15 200IU/0.8mL
Injection, solution Subcutaneous 19 000IU/mL
Injection, solution Subcutaneous 2850IU/0.3mL
Injection, solution Subcutaneous 3800IU/0.4mL
Injection, solution Subcutaneous 5700IU/0.6mL
Injection, solution Subcutaneous 7600IU/0.8mL
Injection, solution Subcutaneous 9500IU/mL
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties Not Available
Predicted Properties Not Available
References
Synthesis Reference Not Available
General Reference
  1. Collignon F, Frydman A, Caplain H, Ozoux ML, Le Roux Y, Bouthier J, Thebault JJ: Comparison of the pharmacokinetic profiles of three low molecular mass heparins—dalteparin, enoxaparin and nadroparin—administered subcutaneously in healthy volunteers (doses for prevention of thromboembolism). Thromb Haemost. 1995 Apr;73(4):630-40. Pubmed
  2. Frydman A: Low-molecular-weight heparins: an overview of their pharmacodynamics, pharmacokinetics and metabolism in humans. Haemostasis. 1996;26 Suppl 2:24-38. Pubmed
  3. Lai KN, Wang AY, Ho K, Szeto CC, Li M, Wong LK, Yu AW: Use of low-dose low molecular weight heparin in hemodialysis. Am J Kidney Dis. 1996 Nov;28(5):721-6. Pubmed
  4. Boneu B, Navarro C, Cambus JP, Caplain H, d’Azemar P, Necciari J, Duret JP, Gaud C, Sie P: Pharmacodynamics and tolerance of two nadroparin formulations (10,250 and 20,500 anti Xa IU x ml(-1)) delivered for 10 days at therapeutic dose. Thromb Haemost. 1998 Feb;79(2):338-41. Pubmed
  5. Laporte S, Mismetti P, Piquet P, Doubine S, Touchot A, Decousus H: Population pharmacokinetic of nadroparin calcium (Fraxiparine) in children hospitalised for open heart surgery. Eur J Pharm Sci. 1999 May;8(2):119-25. Pubmed
  6. Ng HJ, Lee LH: Heparin-induced thrombocytopenia: acknowledging its presence in low-molecular weight heparin therapy. Int J Hematol. 2003 Feb;77(2):185-7. Pubmed
  7. Breddin HK: Prophylaxis and treatment of deep-vein thrombosis. Semin Thromb Hemost. 2000;26 Suppl 1:47-52. Pubmed
  8. Haas SK: Venous thromboembolic risk and its prevention in hospitalized medical patients. Semin Thromb Hemost. 2002 Dec;28(6):577-84. Pubmed
  9. Davis R, Faulds D: Nadroparin calcium. A review of its pharmacology and clinical use in the prevention and treatment of thromboembolic disorders. Drugs Aging. 1997 Apr;10(4):299-322. Pubmed
  10. Iaremchuk AIa, Zotov AS, Cheshuk VE, Anikuc’ko NF, Zakhartseva LM, Diatel MV, Kravchenko AV, Lobanova OE, Sidorchuk OI: [Clinical effectiveness of nadroparin calcium in the surgical treatment of breast cancer]. Vopr Onkol. 2003;49(2):205-8. Pubmed
  11. Vito Vitale F, Rotondo S, Sessa E, Antonelli G, Colina P, Parisi A, Giamo V, Ferrau F: Successful administration of a low dose of calcium nadroparin in patients suffering from pulmonary embolism and brain metastases: a report of two cases. J Oncol Pharm Pract. 2011 Jun;17(2):141-4. Epub 2009 Dec 16. Pubmed
  12. Agnelli G, Gussoni G, Bianchini C, Verso M, Mandala M, Cavanna L, Barni S, Labianca R, Buzzi F, Scambia G, Passalacqua R, Ricci S, Gasparini G, Lorusso V, Bonizzoni E, Tonato M: Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study. Lancet Oncol. 2009 Oct;10(10):943-9. Epub 2009 Aug 31. Pubmed
External Links
Resource Link
ATC Codes
  • B01AB06
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Drotrecogin alfa The potential benefits of drotrecogin alfa should be weighed against an increased risk of bleeding in patients receiving therapeutic doses of low molecular weight heparins such as nadroparin. Monitor for bleeding during concomitant therapy, and immediately stop infusion of drotrecogin if clinically important bleeding occurs. In patients receiving prophylactic heparin doses, consider continuing this during drotrecogin.
Food Interactions
  • Danshen, dong quai, evening primrose oil, gingko, policosanol, willowbark
Targets

1. Antithrombin-III

Pharmacological action: yes
Actions: potentiator

Most important serine protease inhibitor in plasma that regulates the blood coagulation cascade. AT-III inhibits thrombin as well as factors IXa, Xa and XIa. Its inhibitory activity is greatly enhanced in the presence of heparin

Organism class: human
UniProt ID: P01008 Link_out
Gene: SERPINC1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Davis R, Faulds D: Nadroparin calcium. A review of its pharmacology and clinical use in the prevention and treatment of thromboembolic disorders. Drugs Aging. 1997 Apr;10(4):299-322. Pubmed
  2. Frydman A: Low-molecular-weight heparins: an overview of their pharmacodynamics, pharmacokinetics and metabolism in humans. Haemostasis. 1996;26 Suppl 2:24-38. Pubmed

2. P-selectin

Pharmacological action: unknown
Actions: inhibitor

Ca(2+)-dependent receptor for myeloid cells that binds to carbohydrates on neutrophils and monocytes. Mediates the interaction of activated endothelial cells or platelets with leukocytes. The ligand recognized is sialyl-Lewis X

Organism class: human
UniProt ID: P16109 Link_out
Gene: SELP Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Simonis D, Christ K, Alban S, Bendas G: Affinity and kinetics of different heparins binding to P- and L-selectin. Semin Thromb Hemost. 2007 Jul;33(5):534-9. Pubmed
  2. Ludwig RJ, Alban S, Bistrian R, Boehncke WH, Kaufmann R, Henschler R, Gille J: The ability of different forms of heparins to suppress P-selectin function in vitro correlates to their inhibitory capacity on bloodborne metastasis in vivo. Thromb Haemost. 2006 Mar;95(3):535-40. Pubmed

3. Proto-oncogene protein c-fos

Pharmacological action: unknown
Actions: inhibitor

Nuclear phosphoprotein which forms a tight but non- covalently linked complex with the JUN/AP-1 transcription factor. In the heterodimer, c-fos and JUN/AP-1 basic regions each seems to interact with symmetrical DNA half sites. Has a critical function in regulating the development of cells destined to form and maintain the skeleton. It is thought to have an important role in signal transduction, cell proliferation and differentiation

Organism class: human
UniProt ID: P01100 Link_out
Gene: FOS Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Nagy Z, Turcsik V, Blasko G: The effect of LMWH (Nadroparin) on tumor progression. Pathol Oncol Res. 2009 Dec;15(4):689-92. Pubmed
  2. Sustar V, Jansa R, Frank M, Hagerstrand H, Krzan M, Iglic A, Kralj-Iglic V: Suppression of membrane microvesiculation—a possible anticoagulant and anti-tumor progression effect of heparin. Blood Cells Mol Dis. 2009 May-Jun;42(3):223-7. Epub 2009 Mar 3. Pubmed

4. Myc proto-oncogene protein

Pharmacological action: unknown
Actions: inhibitor
UniProt ID: P01106 Link_out

References:
  1. Nagy Z, Turcsik V, Blasko G: The effect of LMWH (Nadroparin) on tumor progression. Pathol Oncol Res. 2009 Dec;15(4):689-92. Pubmed
  2. Sustar V, Jansa R, Frank M, Hagerstrand H, Krzan M, Iglic A, Kralj-Iglic V: Suppression of membrane microvesiculation—a possible anticoagulant and anti-tumor progression effect of heparin. Blood Cells Mol Dis. 2009 May-Jun;42(3):223-7. Epub 2009 Mar 3. Pubmed
Enzymes
Searched, but no enzymes found.
Transporters
Searched, but no transporters found.
Carriers
Searched, but no carriers found.
Comments
Drug created on June 14, 2011 23:17 / Updated on June 19, 2011 17:04