Sulodexide
Identification
- Summary
Sulodexide is a drug used to treat chronic venous ulcers in the legs.
- Generic Name
- Sulodexide
- DrugBank Accession Number
- DB06271
- Background
Sulodexide is a mixture of glycosaminoglycans (GAGs) composed of dermatan sulfate (DS) and fast moving heparin (FMH).
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Thrombolytic agents - Protein Chemical Formula
- Not Available
- Protein Average Weight
- 6500.0 Da (range 5000-8000)
- Sequences
- Not Available
- Synonyms
- Sulodexida
- Sulodexide
- External IDs
- KRX-101
Pharmacology
- Indication
Sulodexide 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.
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- Contraindications & Blackbox Warnings
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- Pharmacodynamics
Sulodexide is extensively absorbed owing to its low molecular weight compared to unfractionated heparin. It offers the potential advantages of a longer half-life and reduced global anticoagulation effects, properties which differ from other glycosaminoglycans. Sulodexide potentiates antithrombin III and heparin cofactor II due to the presence of both glycoaminoglycan fractions. 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 action
Thrombin 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).
Target Actions Organism AHeparin cofactor 2 agonistHumans AAntithrombin-III potentiatorHumans - Absorption
Sulodexide 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 binding
Not Available
- Metabolism
It is mainly metabolized in the liver.
- Route of elimination
Sulodexide 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-life
The 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
- Adverse Effects
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- Toxicity
Sulodexide 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.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The risk or severity of bleeding can be increased when Abciximab is combined with Sulodexide. Acebutolol The risk or severity of hyperkalemia can be increased when Acebutolol is combined with Sulodexide. Aceclofenac The risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Sulodexide. Acemetacin The risk or severity of bleeding and hemorrhage can be increased when Sulodexide is combined with Acemetacin. Acenocoumarol The risk or severity of bleeding can be increased when Acenocoumarol is combined with Sulodexide. Acetylsalicylic acid Acetylsalicylic acid may increase the anticoagulant activities of Sulodexide. Albutrepenonacog alfa The therapeutic efficacy of Albutrepenonacog alfa can be decreased when used in combination with Sulodexide. Alclofenac The risk or severity of bleeding and hemorrhage can be increased when Alclofenac is combined with Sulodexide. Aldesleukin The risk or severity of bleeding can be increased when Sulodexide is combined with Aldesleukin. Alemtuzumab The risk or severity of bleeding can be increased when Sulodexide is combined with Alemtuzumab. Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - Food Interactions
- Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Sulonex / Vessel
Categories
- ATC Codes
- B01AB11 — Sulodexide
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 75HGV0062C
- CAS number
- 57821-29-1
References
- General References
- 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. [Article]
- Harenberg J: Review of pharmacodynamics, pharmacokinetics, and therapeutic properties of sulodexide. Med Res Rev. 1998 Jan;18(1):1-20. [Article]
- 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. doi: 10.2147/JBM.S10558. Epub 2010 Jun 15. [Article]
- Hoppensteadt DA, Fareed J: Pharmacological profile of sulodexide. Int Angiol. 2014 Jun;33(3):229-35. [Article]
- External Links
- KEGG Drug
- D08547
- PubChem Substance
- 347910343
- ChEMBL
- CHEMBL2108086
- Therapeutic Targets Database
- DAP000866
- PharmGKB
- PA164746343
- Wikipedia
- Sulodexide
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Recruiting Treatment Coronavirus Disease 2019 (COVID‑19) / Endothelial Dysfunction / Inflammation / Thrombosis 1 4 Terminated Other Post Thrombotic Syndrome 1 4 Terminated Treatment Diabetic Nephropathy 1 4 Unknown Status Treatment Albuminuria / Diabetic Nephropathy 1 4 Withdrawn Treatment Type 2 Diabetic Nephropathy 1 3 Active Not Recruiting Treatment End Stage Renal Disease (ESRD) / Hemodialysis Treatment / Kidney Failure / Vascular Access 2 3 Completed Treatment Diabetic Nephropathy 1 3 Recruiting Prevention Anticoagulant Therapy / Elderly / Venous Thromboembolism 1 3 Recruiting Treatment Chronic Insufficiency Venous / Chronic Venous Diseases 1 3 Recruiting Treatment Coronavirus Disease 2019 (COVID‑19) / Endothelial Dysfunction / Post-Covid 19 / Thrombosis 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 250 ULS Injection, solution Parenteral 600 ULS/2ML Capsule Oral 250 LRU Injection, solution Intramuscular; Intravenous 600 LRU/2mL Injection, solution Parenteral Capsule Oral 150 U Injection, solution Intramuscular; Intravenous 300 LSU/ml Injection, solution Intramuscular; Intravenous 600 LSU Capsule Oral Injection, solution Intramuscular; Intravenous Capsule Oral 250 LSU Capsule Oral 25.000 mg Solution Parenteral 60.00 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets

- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Serine-type endopeptidase inhibitor activity
- Specific Function
- Thrombin inhibitor activated by the glycosaminoglycans, heparin or dermatan sulfate. In the presence of the latter, HC-II becomes the predominant thrombin inhibitor in place of antithrombin III (AT...
- Gene Name
- SERPIND1
- Uniprot ID
- P05546
- Uniprot Name
- Heparin cofactor 2
- Molecular Weight
- 57070.16 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Potentiator
- General Function
- Serine-type endopeptidase inhibitor activity
- Specific Function
- Most important serine protease inhibitor in plasma that regulates the blood coagulation cascade. AT-III inhibits thrombin, matriptase-3/TMPRSS7, as well as factors IXa, Xa and XIa. Its inhibitory a...
- Gene Name
- SERPINC1
- Uniprot ID
- P01008
- Uniprot Name
- Antithrombin-III
- Molecular Weight
- 52601.935 Da
References
- 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. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Harenberg J: Review of pharmacodynamics, pharmacokinetics, and therapeutic properties of sulodexide. Med Res Rev. 1998 Jan;18(1):1-20. [Article]
Drug created at March 19, 2008 16:20 / Updated at January 28, 2023 16:05