Angioflux Mechanism of Action

Pharmacology: Sulodexide (Angioflux) is a highly purified mixture of glycosaminoglycans consisting of 80% low molecular weight heparin and 20% dermatan sulfate, total components being from porcine origin. Because of the low molecular weights of both fractions, sulodexide (Angioflux) has a more extensive oral absorption compared to unfractionated heparin. Compared to other glycosaminoglycans, sulodexide (Angioflux) has a prolonged half-life and reduced effect on systemic clotting and bleeding. Given orally, subcutaneously, or by intravenous injection, sulodexide (Angioflux) exhibits thrombolytic and fibrinolytic activity thereby demonstrating efficacy in the treatment of thromboembolic disease. These antithrombotic and antithrombin properties are of great pharmacological value and make sulodexide (Angioflux) a suitable drug for the prophylaxis and treatment of arterial and venous peripheral diseases.
The main mechanism can be identified in a dose-dependent inhibition of the activated coagulation factor X, while the limited interference effect with thrombin avoids the consequences of an anticoagulant action. Sulodexide (Angioflux) exerts potent lipolytic activity, as well as activity related to proteoglycan synthesis by smooth muscle cells, associated with suppression of cell proliferation and inhibition of a significant part of atheromatous plaque development. At the same time, sulodexide (Angioflux) inhibits migration of smooth muscle cells towards the innermost layer, as a result of the drug's antithrombin and anti-platelet aggregation effect. The marked efficacy of sulodexide (Angioflux) is derived from its dual action of catalyzing the inhibition of thrombin by antithrombin III (ATIII) and by heparin cofactor II (HCII), with the added advantage of not increasing bleeding. Sulodexide (Angioflux) possesses marked systemic fibrinolytic activity due to the liberation of tissue plasminogen activator (tPA), with marked functional and antigenic reduction of plasminogen activator inhibitor-1 (PAI-1), and a reduction in plasma fibrinogen concentration, favoring the reduction of blood viscosity.
In summary, sulodexide (Angioflux) has a very effective antithrombotic and antithrombin activity, with efficacy and safety demonstrated in a wide range of vascular pathologies.
Pharmacokinetics: Absorption: The pharmacokinetics of sulodexide (Angioflux) in humans after oral administration of a single 50 mg or 100 mg dose in volunteers was evaluated in several studies. After oral administration, sulodexide (Angioflux) undergoes rapid and progressive intestinal absorption, with the presence of two peaks in plasma corresponding to both components (dermatan sulfate and heparan sulfate) and with concentrations of 0.2-1.0 mg/L at 1-10 hours after administration.
After ingestion, sulfated GAGs are absorbed, undergoing significant degradation and loss of the sulfate groups, which in turn reduce the molecular weight of the drug. The desulfated derivates appear in the blood stream up to 3-4 hours after oral administration, accompanying the sulfated fractions for up to 24 hours, with no relevance from a pharmacodynamic point of view.
Observation of the radioactive fraction linked to the unmodified drug indicates that the relative bioavailability of oral sulodexide (Angioflux) is in the range of 40%-60%. Half-life after ingestion of a 50 mg dose is 18.7 ± 4.1 hours, and 25.8 ± 1.9 hours after a 100 mg dose.
Distribution: Sulodexide (Angioflux) undergoes rapid and progressive absorption, reaches high plasma concentrations, and is widely distributed, particularly in the monocellular endothelial layer, making it very interesting as far as blood clotting is concerned. Reduction in plasma concentration not only depends on rapid drug distribution, but also on binding with the endothelial cell receptors in both arteries and veins, due to the affinity of GAGs for this cellular layer. The long half-life of sulodexide (Angioflux) may be due to the progressive liberation of products linked to these cells, and explains the long-term persistence of the drug in plasma. It is also possible that this process is influenced by metabolic degradation, reducing its affinity for cell receptors. Tissue uptake occurs via the extracellular matrix, as well as the renal and hepatic parenchyma.
Elimination: Sulodexide (Angioflux) is eliminated via the renal, bile, and fecal routes. Renal excretion is the main route, accounting for 55.3 ± 2.9% of drug excreted over 96 hours. A large part of the radioactivity excreted after 48 hours corresponds to degradation products as a result of intracellular biotransformation. Biliary excretion accounts for 23.5 ± 2.3% of the dose removed within 48 hours, and the remaining amount is eliminated by feces, accounting for 23.5 ± 2.8% at 48 hours.