You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
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 354e4808da70a5bd16896d40d8e7c4c304b2c46d0efa4be7aa608033bb036952
Protein chemical formulaNot Available
Protein average weight5000-8000 Da
Sequences
SynonymsNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
SulonexNot Available
VesselNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number57821-29-1
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot 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
ATC CodesB01AB11
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AbciximabAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
AcarboseAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
AcenocoumarolMay enhance the anticoagulant effect of other Anticoagulants.
Acetylsalicylic acidAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
AlbiglutideAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
AlogliptinAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
AlteplaseThrombolytic Agents may enhance the anticoagulant effect of Anticoagulants.
Aminosalicylic AcidSalicylates may enhance the anticoagulant effect of Anticoagulants.
AnagrelideAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
ApixabanApixaban may enhance the anticoagulant effect of Anticoagulants.
ArgatrobanMay enhance the anticoagulant effect of other Anticoagulants.
Bismuth SubsalicylateSalicylates may enhance the anticoagulant effect of Anticoagulants.
BivalirudinMay enhance the anticoagulant effect of other Anticoagulants.
BromocriptineAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
CanagliflozinAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
CelecoxibNonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Anticoagulants.
ChlorpropamideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
CilostazolAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
CitalopramAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
ClopidogrelAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
Cyproterone acetateProgestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
Dabigatran etexilateDabigatran Etexilate may enhance the anticoagulant effect of Anticoagulants.
DalteparinMay enhance the anticoagulant effect of other Anticoagulants.
DanaparoidMay enhance the anticoagulant effect of other Anticoagulants.
DapagliflozinAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
DasatinibDasatinib may enhance the anticoagulant effect of Anticoagulants.
DeferasiroxMay enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased.
DesogestrelEstrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
DesvenlafaxineAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
DiflunisalAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
DipyridamoleAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
DisopyramideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
DrospirenoneEstrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
DulaglutideAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
DuloxetineAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
EmpagliflozinAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
EnoxaparinMay enhance the anticoagulant effect of other Anticoagulants.
EpoprostenolProstacyclin Analogues may enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination.
EptifibatideAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
EscitalopramAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
EstropipateEstrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
Ethinyl EstradiolEstrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
EthynodiolEstrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
EtodolacAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
EtonogestrelProgestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
ExenatideAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
FenoprofenAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
FloctafenineAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
FluoxetineAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
FluvoxamineAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
Fondaparinux sodiumMay enhance the anticoagulant effect of other Anticoagulants.
GliclazideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
GlimepirideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
GlipizideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
GlyburideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
HeparinMay enhance the anticoagulant effect of other Anticoagulants.
HomoharringtonineMay enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased.
IbritumomabMay enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to an increased risk of bleeding.
IbuprofenAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
IcosapentOmega-3 Fatty Acids may enhance the anticoagulant effect of Anticoagulants.
Icosapent ethylOmega-3 Fatty Acids may enhance the anticoagulant effect of Anticoagulants.
IloprostProstacyclin Analogues may enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination.
IndomethacinAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
inhaled insulinMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
Insulin AspartMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
Insulin DetemirMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
Insulin GlargineMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
Insulin GlulisineMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
Insulin LisproMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
Insulin RegularMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
KetoprofenAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
KetorolacAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
LanreotideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
LevomilnacipranAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
LevonorgestrelProgestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
LinagliptinAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
LiraglutideAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
Magnesium salicylateSalicylates may enhance the anticoagulant effect of Anticoagulants.
MecaserminMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
Medroxyprogesterone AcetateProgestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
Mefenamic acidAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
Megestrol acetateProgestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
MeloxicamAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
MestranolEstrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
MetforminAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
MifepristoneMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
MiglitolAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
MilnacipranAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
NabumetoneAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
NadroparinMay enhance the anticoagulant effect of other Anticoagulants.
NaproxenAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
NateglinideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
NorelgestrominEstrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
NorethindroneProgestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
NorgestimateEstrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
ObinutuzumabMay enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased.
OctreotideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
OxaprozinAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
ParoxetineAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
PasireotideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
PentamidineMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
Pentosan PolysulfatePentosan Polysulfate Sodium may enhance the anticoagulant effect of Anticoagulants.
PioglitazoneAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
PiperazineEstrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
PiroxicamAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
PramlintideAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
PrasugrelAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
ProgesteroneProgestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
QuinineMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
RepaglinideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
ReteplaseThrombolytic Agents may enhance the anticoagulant effect of Anticoagulants.
RivaroxabanMay enhance the anticoagulant effect of Rivaroxaban.
RosiglitazoneAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
SalsalateSalicylates may enhance the anticoagulant effect of Anticoagulants.
SaxagliptinAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
SertralineAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
SitagliptinAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
SulfadiazineMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
SulfamethoxazoleMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
SulfisoxazoleMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
SulindacAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
SunitinibMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
TenecteplaseThrombolytic Agents may enhance the anticoagulant effect of Anticoagulants.
Tiaprofenic acidAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
TicagrelorAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
TiclopidineAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
TinzaparinMay enhance the anticoagulant effect of other Anticoagulants.
TipranavirTipranavir may enhance the anticoagulant effect of Anticoagulants.
TirofibanAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
TolazamideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
TolbutamideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
TolmetinAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
TositumomabMay enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse effects may be increased.
TreprostinilProstacyclin Analogues may enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination.
VenlafaxineAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
VilazodoneAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
Vitamin EVitamin E may enhance the anticoagulant effect of Anticoagulants. Vitamin E may also increase the overall risk for bleeding.
VorapaxarVorapaxar may enhance the adverse/toxic effect of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding.
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

Comments
comments powered by Disqus
Drug created on March 19, 2008 10:20 / Updated on September 30, 2014 00:18