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Identification
NameNadroparin
Accession NumberDB08813
TypeSmall Molecule
GroupsApproved
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
SynonymsNot Available
SaltsNot Available
Brand namesNot 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
IndicationNadroparin 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
PharmacodynamicsNadroparin 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 actionThe 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.
AbsorptionAbsorption is linear. The bioavailability of nadroparin after subcutaneous administration is about 89%.
Volume of distribution

3.59L

Protein bindingMuch lower compared to heparin, which has over 90% protein bound.
Metabolism

Nadroparin is metabolized in the liver.

Route of eliminationNadroparin is eliminated via the kidneys through non-saturable mechanisms.
Half lifeIn 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

ToxicityOsteopenia 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 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
Injection, solutionSubcutaneous11 400IU/0.6mL
Injection, solutionSubcutaneous15 200IU/0.8mL
Injection, solutionSubcutaneous19 000IU/mL
Injection, solutionSubcutaneous2850IU/0.3mL
Injection, solutionSubcutaneous3800IU/0.4mL
Injection, solutionSubcutaneous5700IU/0.6mL
Injection, solutionSubcutaneous7600IU/0.8mL
Injection, solutionSubcutaneous9500IU/mL
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Predicted PropertiesNot Available
Spectra
SpectraNot Available
References
Synthesis ReferenceNot 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
ResourceLink
ATC CodesB01AB06
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
Drotrecogin alfaThe 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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Antithrombin-III P01008 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
P-selectin P16109 Details

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 c-Fos

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Proto-oncogene c-Fos P01100 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Myc proto-oncogene protein P01106 Details

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

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Drug created on June 14, 2011 23:17 / Updated on June 19, 2011 17:04