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Identification
NameDalteparin
Accession NumberDB06779
TypeSmall Molecule
GroupsApproved
Description

Dalteparin, a low molecular weight heparin (LMWH) prepared by nitrous acid degradation of unfractionated heparin of porcine intestinal mucosa origin, is an anticoagulant. It is composed of strongly acidic sulphated polysaccharide chains with an average molecular weight of 5000 and about 90% of the material within the range of 2000-9000. LMWHs have a more predictable response, a greater bioavailability, and a longer anti-Xa half life than unfractionated heparin. Dalteparin can also be safely used in most pregnant women. Low molecular weight heparins are less effective at inactivating factor IIa due to their shorter length compared to unfractionated heparin.

Structure
Thumb
Synonyms
SynonymLanguageCode
DaltepariininatriumNot AvailableNot Available
Dalteparin sodná sůlNot AvailableNot Available
Dalteparin SodyumNot AvailableNot Available
Dalteparin-nátriumNot AvailableNot Available
Dalteparina sódicaNot AvailableNot Available
Daltéparine sodiqueNot AvailableNot Available
DalteparinnatriumNot AvailableNot Available
Dalteparino natrio druskaNot AvailableNot Available
Dalteparinum NatricumNot AvailableNot Available
Dalteparyna sodowaNot AvailableNot Available
Heparin Fragment KABI 2165Not AvailableNot Available
TedelparinNot AvailableNot Available
Salts
Name/CAS Structure Properties
Dalteparin sodium
Thumb
  • InChI Key: OHJKXVLJWUPWQG-IUYNYSEKSA-N
  • Monoisotopic Mass: 594.981904187
  • Average Mass: 595.485
DBSALT000779
Brand names
NameCompany
BoxolPharmacia
EurodalGland
FragminPfizer
LigoframinPfizer
Low LiquemineRoche
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
IndicationDalteparin is used as a prophylaxis for deep-vein thrombosis and pulmonary embolisms in patients undergoing general surgery (e.g., abdominal, gynecologic, urologic), and in patients with acute medical conditions (e.g. cancer, bed rest, heart failure, severe lung disease). It is also used in patients who have severely restricted mobility, which poses a risk for thromboembolic complications. Dalteparin is also used concomitantly with aspirin and/or other therapy (e.g., nitrates, β-adrenergic blockers, clopidogrel, platelet glycoprotein [GP] IIb/IIIa-receptor inhibitors) to reduce the risk of acute cardiac ischemic events. The patients who undergo this treatment combination have unstable angina or non-ST-segment elevation/non-Q-wave myocardial infarction (i.e., non-ST-segment elevation acute coronary syndromes). It is also used in the prevention of clotting during hemodialysis and hemofiltration in connection with acute renal failure or chronic renal insufficiency.
PharmacodynamicsDalteparin has an antithrombin binding site that is essential for high affinity binding to the plasma protein antithrombin (ATIII). Anti-Xa activity of plasma is used as both as an estimate of clotting activity, and as a basis to determine dosage. Its use should be avoided in patients with a creatinine clearance less than 20mL/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 actionDalteparin potentiates the activity of ATIII, inhibiting the formation of both factor Xa and thrombin. The main difference between dalteparin and unfractionated heparin (UH) is that dalteparin preferentially inactivates factor Xa. As a result, only a slight increase in clotting time [(i.e. activated partial thomboplastin time (APTT)] is observed relative to UH. For this same reason, APTT is not used to monitor the effects of dalteparin except as an indicator for overdosage.
AbsorptionAlmost completely absorbed after subcutaneous (sc) doses, with a bioavialability of about 87%.
Volume of distribution

3 litres

Protein bindingLess than unfractionated heparin, which is more than 90%.
Metabolism

Liver and the reticulo-endothelial system are the sites of biotransformation. They are partially metabolized by desulphatation and depolymerization.

Route of eliminationAfter 4 hours, about 20% is seen in urine. Most of the remainder is found in the liver, gastrointestinal tract and kidney. The kidneys are the major site of dalteparin excretion (approximately 70% based on animal studies).
Half lifeTerminal Half life: Intravenous - 2 hours. Subcutaneous - 3-5hours
Clearance

Excreted via kidneys. The plasma clearance rate is 33 mL/min.

ToxicityOverdosage: hemorrhagic complications. Adverse Drug Reaction: (common) osteopenia with extended use; mild, reversible non-immunological thrombocytopenia; transient elevation of liver transaminases; alopecia. (uncommon): severe immunologically-mediated heparin-induced thrombocytopenia; anaphylactic reactions; skin rash, skin necrosis; retroperitoneal hemorrhage; angioedema
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
Manufacturers
  • Pfizer inc
  • Gland pharma ltd
  • Roche
  • Pharmacia corp
PackagersNot Available
Dosage forms
FormRouteStrength
InjectionParenteral10 000IU/0.4mL
InjectionParenteral12 500IU/0.5mL
InjectionParenteral15 000IU/0.6mL
InjectionParenteral18 000IU/0.72mL
InjectionParenteral2500IU/0.2mL
InjectionParenteral5000IU/0.2mL
InjectionParenteral7500IU/0.3mL
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Predicted PropertiesNot Available
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. King DJ, Kelton JG: Heparin-associated thrombocytopenia. Ann Intern Med. 1984 Apr;100(4):535-40. Pubmed
  2. Bell WR, Royall RM: Heparin-associated thrombocytopenia: a comparison of three heparin preparations. N Engl J Med. 1980 Oct 16;303(16):902-7. Pubmed
  3. Ockelford PA, Patterson J, Johns AS: A double-blind randomized placebo controlled trial of thromboprophylaxis in major elective general surgery using once daily injections of a low molecular weight heparin fragment (Fragmin). Thromb Haemost. 1989 Dec 29;62(4):1046-9. Pubmed
  4. Hartl P, Brucke P, Dienstl E, Vinazzer H: Prophylaxis of thromboembolism in general surgery: comparison between standard heparin and Fragmin. Thromb Res. 1990 Feb 15;57(4):577-84. Pubmed
  5. Monreal M, Lafoz E, Salvador R, Roncales J, Navarro A: Adverse effects of three different forms of heparin therapy: thrombocytopenia, increased transaminases, and hyperkalaemia. Eur J Clin Pharmacol. 1989;37(4):415-8. Pubmed
  6. Holmer E, Soderberg K, Bergqvist D, Lindahl U: Heparin and its low molecular weight derivatives: anticoagulant and antithrombotic properties. Haemostasis. 1986;16 Suppl 2:1-7. Pubmed
  7. Malm K, Dahlback B, Arnljots B: Low-molecular-weight heparin (dalteparin) effectively prevents thrombosis in a rat model of deep arterial injury. Plast Reconstr Surg. 2003 Apr 15;111(5):1659-66. Pubmed
  8. Tincani E, Mannucci C, Casolari B, Turrini F, Crowther MA, Prisco D, Cenci AM, Bondi M: Safety of dalteparin for the prophylaxis of venous thromboembolism in elderly medical patients with renal insufficiency: a pilot study. Haematologica. 2006 Jul;91(7):976-9. Epub 2006 Jun 1. Pubmed
  9. Schmid P, Brodmann D, Fischer AG, Wuillemin WA: Study of bioaccumulation of dalteparin at a prophylactic dose in patients with various degrees of impaired renal function. J Thromb Haemost. 2009 Apr;7(4):552-8. Epub 2009 Jan 19. Pubmed
  10. Abe W, Ikejima K, Lang T, Okumura K, Enomoto N, Kitamura T, Takei Y, Sato N: Low molecular weight heparin prevents hepatic fibrogenesis caused by carbon tetrachloride in the rat. J Hepatol. 2007 Feb;46(2):286-94. Epub 2006 Oct 25. Pubmed
  11. Frydman A: Low-molecular-weight heparins: an overview of their pharmacodynamics, pharmacokinetics and metabolism in humans. Haemostasis. 1996;26 Suppl 2:24-38. Pubmed
  12. Samama MM, Gerotziafas GT: Comparative pharmacokinetics of LMWHs. Semin Thromb Hemost. 2000;26 Suppl 1:31-8. Pubmed
  13. Rey E, Rivard GE: Prophylaxis and treatment of thromboembolic diseases during pregnancy with dalteparin. Int J Gynaecol Obstet. 2000 Oct;71(1):19-24. Pubmed
External Links
ResourceLink
KEGG DrugD03353
WikipediaDalteparin_sodium
ATC CodesB01AB04
AHFS Codes
  • 20:12.04.16
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
Drotrecogin alfaLow molecular weight heparin (LMWH) such as dalteparin may enhance the adverse/toxic effect of drotrecogin alfa. Bleeding may occur.
Food Interactions
  • Herbs (anticoagulant/antiplatelet properties such as ginseng, ginkgo, ginger, garlic)

Targets

1. Antithrombin-III

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Antithrombin-III P01008 Details

References:

  1. 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. Rey E, Rivard GE: Prophylaxis and treatment of thromboembolic diseases during pregnancy with dalteparin. Int J Gynaecol Obstet. 2000 Oct;71(1):19-24. Pubmed

2. Vascular endothelial growth factor A

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Vascular endothelial growth factor A P15692 Details

References:

  1. Norrby K, Nordenhem A: Dalteparin, a low-molecular-weight heparin, promotes angiogenesis mediated by heparin-binding VEGF-A in vivo. APMIS. 2010 Dec;118(12):949-57. doi: 10.1111/j.1600-0463.2010.02635.×. Epub 2010 Oct 12. Pubmed
  2. Marchetti M, Vignoli A, Russo L, Balducci D, Pagnoncelli M, Barbui T, Falanga A: Endothelial capillary tube formation and cell proliferation induced by tumor cells are affected by low molecular weight heparins and unfractionated heparin. Thromb Res. 2008;121(5):637-45. Epub 2007 Aug 10. Pubmed
  3. Takahashi H, Ebihara S, Okazaki T, Asada M, Sasaki H, Yamaya M: A comparison of the effects of unfractionated heparin, dalteparin and danaparoid on vascular endothelial growth factor-induced tumour angiogenesis and heparanase activity. Br J Pharmacol. 2005 Oct;146(3):333-43. Pubmed

3. Tissue factor pathway inhibitor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Tissue factor pathway inhibitor P10646 Details

References:

  1. Mousa SA: Low-molecular-weight heparins in thrombosis and cancer: emerging links. Cardiovasc Drug Rev. 2004 Summer;22(2):121-34. Pubmed
  2. Naumnik B, Rydzewska-Rosolowska A, Mysliwiec M: Different Effects of Enoxaparin, Nadroparin, and Dalteparin on Plasma TFPI During Hemodialysis: A Prospective Crossover Randomized Study. Clin Appl Thromb Hemost. 2010 Aug 3. Pubmed
  3. Bendz B, Andersen TO, Sandset PM: Dose-dependent release of endogenous tissue factor pathway inhibitor by different low molecular weight heparins. Blood Coagul Fibrinolysis. 2000 Jun;11(4):343-8. Pubmed

4. P-selectin

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
P-selectin P16109 Details

References:

  1. Rey E, Rivard GE: Prophylaxis and treatment of thromboembolic diseases during pregnancy with dalteparin. Int J Gynaecol Obstet. 2000 Oct;71(1):19-24. Pubmed

Enzymes

1. Heparanase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Heparanase Q9Y251 Details

References:

  1. Takahashi H, Ebihara S, Okazaki T, Asada M, Sasaki H, Yamaya M: A comparison of the effects of unfractionated heparin, dalteparin and danaparoid on vascular endothelial growth factor-induced tumour angiogenesis and heparanase activity. Br J Pharmacol. 2005 Oct;146(3):333-43. Pubmed

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Drug created on September 14, 2010 10:21 / Updated on June 19, 2011 17:03