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Identification
NameSulodexide
Accession NumberDB06271
TypeBiotech
GroupsApproved, Investigational
Description

Sulodexide is a mixture of glycosaminoglycans (GAGs) composed of dermatan sulfate (DS) and fast moving heparin (FMH).

Protein structureNo structure small
Protein chemical formulaNot Available
Protein average weight5000-8000 Da
Sequences
SynonymsNot Available
SaltsNot Available
Brand names
NameCompany
SulonexNot Available
VesselNot Available
Brand mixturesNot Available
Categories
CAS number57821-29-1
Taxonomy
KingdomNot Available
SuperclassNot Available
ClassNot Available
SubclassNot Available
Direct parentNot Available
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationSulodexide has been used clinically for the prophylaxis and treatment of vascular diseases with increased risk of thrombosis, including intermittent claudication, peripheral arterial occlusive disease and post-myocardial infarc-tion. Also investigated in the treatment of diabetic kidney disease and diabetic neuropathy. New anti-inflammatory properties have also extended its use in venous disease.
PharmacodynamicsThe low molecular weight of both sulodexide fractions allows for extensive oral absorption compared to unfractionated heparin. The pharmacological effects of sulodexide differ substantially from other glycosaminoglycans and are mainly characterized by a prolonged half-life and reduced effect on global coagulation and bleeding parameters. Due to the presence of both glycosaminoglycan fractions, sulodexide potentiates the antiprotease activities of both antithrombin III and heparin cofactor II simultaneously. It is capable of inhibiting both anti-IIa and anti-Xa. It promotes fibrinolytic activity by releasing tissue plasminogen activator and reduces plasminogen activator inhibitor. The drug also blocks platelet adhesion and platelet function induced by cathepsin G and thrombin. Research has also shown that Sulodexide had endothelial protective properties by inducing the overexpression of growth factors important for the protection of organs. It has anti-inflammatory properties via its effect on the release of inflammatory mediators from macrophages. This results in anti-proliferative effects such as the regulation of growth factors like VEGF and FGF. The intravenous administration has also been shown capable of releasing tissue factor pathway inhibitor from the endothelium, which also contributes to the anti-thrombotic effects of Sulodexide. Lastly, this drug is known for its ability to inhibit the secretion of MMPs, particularly MMP-9, from leukocytes in a dose dependent manner, resulting in the restoration of the balance with their tissue inhibitors.
Mechanism of actionThrombin inhibition produced by sulodexide is due to the additive effect of its components, namely, heparin cofactor II (HCII) catalysis by dermatan sulfate and antithrombin-III catalysis by fast moving heparin (FMH).
AbsorptionSulodexide can be administered via the oral route, IV and IM routes. After oral dosing, the absorption rate being equivalent, the bioavailability is 40-60%. either calculated from the fast-moving heparin fraction or from the dermatan fraction. Bioavailability following IM administration is approximately 90%. After a rapid absorption in the intestine, the dermatan and heparin components start to appear in the plasma. Sulodexide is degraded after ingestion and loses its sulfate groups and both sulfated and unsulfated groups circulate in the blood for up to 24hours. AUC=22.83+/-4.44mg.h/L.
Volume of distribution

Cmax=516+/-77.54ng/mL,
Tmax=1.33+/-0.58h,
Vd=71.24+/-14.06L (b phase).
Sulodexide reaches high concentrations in the plasma and is widely distributed in the endothelial layer. Binding to endothelial cell receptors in arteries and veins contributes to its rapid distribution profile.

Protein bindingNot Available
Metabolism

It is mainly metabolized in the liver.

Route of eliminationSulodexide is eliminated via the renal, fecal and bile routes. The main clearance occurs renally and accounts for elimination of 55+2.9% of the drug over 96 hours. The fecal and bile routes remove the rest of the drug over 48 hours, which accounts for 23.5+/-2.5% for both routes.
Half lifeThe elimination half-life was 11.7 +/- 2.0 h after intravenous administration, 18.7 +/- 4.1 h after 50 mg per os, and 25.8 +/- 1.9 h after 100 mg per os.
Clearance

2.70+/-0.58L/h

ToxicitySulodexide seems to be well tolerated. Most adverse effects reported are related to the GI system and seem to be transient in nature. Among others adverse reactions are diarrhea, epigastralgia, dyspepsia, heartburn and dizziness. Allergic reactions, such as skin rash, have also been reported but are very rare.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Cosmi B, Cini M, Legnani C, Pancani C, Calanni F, Coccheri S: Additive thrombin inhibition by fast moving heparin and dermatan sulfate explains the anticoagulant effect of sulodexide, a natural mixture of glycosaminoglycans. Thromb Res. 2003 Mar 15;109(5-6):333-9. Pubmed
    #Lasierra-Cirujeda J, Coronel P, Aza M, Gimeno M. Use of sulodexide in patients with peripheral vascular disease. J Blood Med. 2010;1:105-15. PMID: 22282689
  2. Harenberg J: Review of pharmacodynamics, pharmacokinetics, and therapeutic properties of sulodexide. Med Res Rev. 1998 Jan;18(1):1-20. Pubmed
    #Hoppensteadt DA, Fareed J. Pharmacological profile of sulodexide. Int Angiol. 2014 Jun;33(3):229-35. PMID:24936531
External Links
ResourceLink
PharmGKBPA164746343
WikipediaSulodexide
ATC CodesB01AB11
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Heparin cofactor 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Heparin cofactor 2 P05546 Details

References:

  1. Cosmi B, Cini M, Legnani C, Pancani C, Calanni F, Coccheri S: Additive thrombin inhibition by fast moving heparin and dermatan sulfate explains the anticoagulant effect of sulodexide, a natural mixture of glycosaminoglycans. Thromb Res. 2003 Mar 15;109(5-6):333-9. Pubmed

2. Antithrombin-III

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Antithrombin-III P01008 Details

References:

  1. Cosmi B, Cini M, Legnani C, Pancani C, Calanni F, Coccheri S: Additive thrombin inhibition by fast moving heparin and dermatan sulfate explains the anticoagulant effect of sulodexide, a natural mixture of glycosaminoglycans. Thromb Res. 2003 Mar 15;109(5-6):333-9. Pubmed
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  3. Harenberg J: Review of pharmacodynamics, pharmacokinetics, and therapeutic properties of sulodexide. Med Res Rev. 1998 Jan;18(1):1-20. Pubmed

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Drug created on March 19, 2008 10:20 / Updated on September 30, 2014 00:18