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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 354e4808da70a5bd16896d40d8e7c4c304b2c46d0efa4be7aa608033bb036952
Protein chemical formulaNot Available
Protein average weight6500.0 Da (range 5000-8000)
Sequences
SynonymsNot Available
External Identifiers
  • KRX-101
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 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
    #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
AbciximabAbciximab may increase the anticoagulant activities of Sulodexide.
AcenocoumarolSulodexide may increase the anticoagulant activities of Acenocoumarol.
Acetylsalicylic acidAcetylsalicylic acid may increase the anticoagulant activities of Sulodexide.
AlteplaseAlteplase may increase the anticoagulant activities of Sulodexide.
Aminosalicylic AcidAminosalicylic Acid may increase the anticoagulant activities of Sulodexide.
AnagrelideAnagrelide may increase the anticoagulant activities of Sulodexide.
ApixabanApixaban may increase the anticoagulant activities of Sulodexide.
ArgatrobanSulodexide may increase the anticoagulant activities of Argatroban.
Bismuth SubsalicylateBismuth Subsalicylate may increase the anticoagulant activities of Sulodexide.
BivalirudinSulodexide may increase the anticoagulant activities of Bivalirudin.
CaffeineCaffeine may increase the anticoagulant activities of Sulodexide.
CangrelorCangrelor may increase the anticoagulant activities of Sulodexide.
CelecoxibCelecoxib may increase the anticoagulant activities of Sulodexide.
CilostazolCilostazol may increase the anticoagulant activities of Sulodexide.
CitalopramCitalopram may increase the anticoagulant activities of Sulodexide.
ClopidogrelClopidogrel may increase the anticoagulant activities of Sulodexide.
Collagenase clostridium histolyticumThe risk or severity of adverse effects can be increased when Sulodexide is combined with Collagenase clostridium histolyticum.
Cyproterone acetateThe therapeutic efficacy of Sulodexide can be decreased when used in combination with Cyproterone acetate.
Dabigatran etexilateDabigatran etexilate may increase the anticoagulant activities of Sulodexide.
DalteparinSulodexide may increase the anticoagulant activities of Dalteparin.
DanaparoidSulodexide may increase the anticoagulant activities of Danaparoid.
DasatinibDasatinib may increase the anticoagulant activities of Sulodexide.
DeferasiroxThe risk or severity of adverse effects can be increased when Sulodexide is combined with Deferasirox.
Deoxycholic AcidThe risk or severity of adverse effects can be increased when Sulodexide is combined with Deoxycholic Acid.
DesirudinSulodexide may increase the anticoagulant activities of Desirudin.
DesogestrelDesogestrel may decrease the anticoagulant activities of Sulodexide.
DesvenlafaxineDesvenlafaxine may increase the anticoagulant activities of Sulodexide.
DiclofenacDiclofenac may increase the anticoagulant activities of Sulodexide.
DienogestThe therapeutic efficacy of Sulodexide can be decreased when used in combination with Dienogest.
DiflunisalDiflunisal may increase the anticoagulant activities of Sulodexide.
DihydrocodeineDihydrocodeine may increase the anticoagulant activities of Sulodexide.
DipyridamoleDipyridamole may increase the anticoagulant activities of Sulodexide.
DrospirenoneDrospirenone may decrease the anticoagulant activities of Sulodexide.
DuloxetineDuloxetine may increase the anticoagulant activities of Sulodexide.
EdoxabanEdoxaban may increase the anticoagulant activities of Sulodexide.
EnoxaparinSulodexide may increase the anticoagulant activities of Enoxaparin.
EpoprostenolThe risk or severity of adverse effects can be increased when Epoprostenol is combined with Sulodexide.
EptifibatideEptifibatide may increase the anticoagulant activities of Sulodexide.
EscitalopramEscitalopram may increase the anticoagulant activities of Sulodexide.
EstradiolEstradiol may decrease the anticoagulant activities of Sulodexide.
EstropipateEstropipate may decrease the anticoagulant activities of Sulodexide.
Ethinyl EstradiolEthinyl Estradiol may decrease the anticoagulant activities of Sulodexide.
EthynodiolEthynodiol may decrease the anticoagulant activities of Sulodexide.
EtodolacEtodolac may increase the anticoagulant activities of Sulodexide.
EtonogestrelThe therapeutic efficacy of Sulodexide can be decreased when used in combination with Etonogestrel.
FenoprofenFenoprofen may increase the anticoagulant activities of Sulodexide.
FloctafenineFloctafenine may increase the anticoagulant activities of Sulodexide.
FluoxetineFluoxetine may increase the anticoagulant activities of Sulodexide.
FlurbiprofenFlurbiprofen may increase the anticoagulant activities of Sulodexide.
FluvoxamineFluvoxamine may increase the anticoagulant activities of Sulodexide.
Fondaparinux sodiumSulodexide may increase the anticoagulant activities of Fondaparinux sodium.
HeparinSulodexide may increase the anticoagulant activities of Heparin.
Hydroxyprogesterone caproateThe therapeutic efficacy of Sulodexide can be decreased when used in combination with Hydroxyprogesterone caproate.
IbritumomabThe risk or severity of adverse effects can be increased when Sulodexide is combined with Ibritumomab.
IbrutinibThe risk or severity of adverse effects can be increased when Ibrutinib is combined with Sulodexide.
IbuprofenIbuprofen may increase the anticoagulant activities of Sulodexide.
IcosapentIcosapent may increase the anticoagulant activities of Sulodexide.
Icosapent ethylIcosapent ethyl may increase the anticoagulant activities of Sulodexide.
IloprostThe risk or severity of adverse effects can be increased when Iloprost is combined with Sulodexide.
IndomethacinIndomethacin may increase the anticoagulant activities of Sulodexide.
KetoprofenKetoprofen may increase the anticoagulant activities of Sulodexide.
KetorolacKetorolac may increase the anticoagulant activities of Sulodexide.
LevomilnacipranLevomilnacipran may increase the anticoagulant activities of Sulodexide.
LevonorgestrelThe therapeutic efficacy of Sulodexide can be decreased when used in combination with Levonorgestrel.
Magnesium salicylateMagnesium salicylate may increase the anticoagulant activities of Sulodexide.
Medroxyprogesterone AcetateThe therapeutic efficacy of Sulodexide can be decreased when used in combination with Medroxyprogesterone Acetate.
Mefenamic acidMefenamic acid may increase the anticoagulant activities of Sulodexide.
Megestrol acetateThe therapeutic efficacy of Sulodexide can be decreased when used in combination with Megestrol acetate.
MeloxicamMeloxicam may increase the anticoagulant activities of Sulodexide.
MestranolMestranol may decrease the anticoagulant activities of Sulodexide.
MilnacipranMilnacipran may increase the anticoagulant activities of Sulodexide.
NabumetoneNabumetone may increase the anticoagulant activities of Sulodexide.
NadroparinSulodexide may increase the anticoagulant activities of Nadroparin.
NaproxenNaproxen may increase the anticoagulant activities of Sulodexide.
NintedanibThe risk or severity of adverse effects can be increased when Sulodexide is combined with Nintedanib.
NorethindroneThe therapeutic efficacy of Sulodexide can be decreased when used in combination with Norethindrone.
NorgestimateNorgestimate may decrease the anticoagulant activities of Sulodexide.
ObinutuzumabThe risk or severity of adverse effects can be increased when Sulodexide is combined with Obinutuzumab.
Omega-3 fatty acidsOmega-3 fatty acids may increase the anticoagulant activities of Sulodexide.
Omega-3-acid ethyl estersOmega-3-acid ethyl esters may increase the anticoagulant activities of Sulodexide.
OxaprozinOxaprozin may increase the anticoagulant activities of Sulodexide.
ParoxetineParoxetine may increase the anticoagulant activities of Sulodexide.
Pentosan PolysulfatePentosan Polysulfate may increase the anticoagulant activities of Sulodexide.
PiroxicamPiroxicam may increase the anticoagulant activities of Sulodexide.
PrasugrelPrasugrel may increase the anticoagulant activities of Sulodexide.
ProgesteroneThe therapeutic efficacy of Sulodexide can be decreased when used in combination with Progesterone.
ReteplaseReteplase may increase the anticoagulant activities of Sulodexide.
RivaroxabanSulodexide may increase the anticoagulant activities of Rivaroxaban.
SalsalateSalsalate may increase the anticoagulant activities of Sulodexide.
SertralineSertraline may increase the anticoagulant activities of Sulodexide.
SulindacSulindac may increase the anticoagulant activities of Sulodexide.
TenecteplaseTenecteplase may increase the anticoagulant activities of Sulodexide.
Tiaprofenic acidTiaprofenic acid may increase the anticoagulant activities of Sulodexide.
TicagrelorTicagrelor may increase the anticoagulant activities of Sulodexide.
TiclopidineTiclopidine may increase the anticoagulant activities of Sulodexide.
TinzaparinSulodexide may increase the anticoagulant activities of Tinzaparin.
TipranavirTipranavir may increase the anticoagulant activities of Sulodexide.
TirofibanTirofiban may increase the anticoagulant activities of Sulodexide.
TolmetinTolmetin may increase the anticoagulant activities of Sulodexide.
TositumomabThe risk or severity of adverse effects can be increased when Sulodexide is combined with Tositumomab.
TreprostinilThe risk or severity of adverse effects can be increased when Treprostinil is combined with Sulodexide.
VenlafaxineVenlafaxine may increase the anticoagulant activities of Sulodexide.
VilazodoneVilazodone may increase the anticoagulant activities of Sulodexide.
Vitamin EVitamin E may increase the anticoagulant activities of Sulodexide.
VorapaxarThe risk or severity of adverse effects can be increased when Vorapaxar is combined with Sulodexide.
VortioxetineVortioxetine may increase the anticoagulant activities of Sulodexide.
WarfarinSulodexide may increase the anticoagulant activities of Warfarin.
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 January 11, 2016 12:30