Noxadium 4000/Noxadium 6000 Mechanism of Action

Pharmacotherapeutic group: Antithrombotic agent, heparin group.
Pharmacology: Pharmacodynamics: Noxadium 4000: Pharmacodynamic effects: Enoxaparin is a LMWH with a mean molecular weight of approximately 4,500 daltons, in which the antithrombotic and anticoagulant activities of standard heparin have been dissociated. The drug substance is the sodium salt. In the in vitro purified system, enoxaparin sodium has a high anti-Xa activity (approximately 100 IU/mg) and low anti-IIa or anti thrombin activity (approximately 28 IU/mg), with a ratio of 3.6. These anticoagulant activities are mediated through anti-thrombin III (ATIII) resulting in anti-thrombotic activities in humans.
Beyond its anti-Xa/IIa activity, further antithrombotic and anti-inflammatory properties of enoxaparin have been identified in healthy subjects and patients as well as in non-clinical models. These include ATIII-dependent inhibition of other coagulation factors like factor VIIa, induction of endogenous Tissue Factor Pathway Inhibitor (TFPI) release as well as a reduced release of von Willebrand factor (vWF) from the vascular endothelium into the blood circulation. These factors are known to contribute to the overall antithrombotic effect of enoxaparin sodium. When used as prophylactic treatment, enoxaparin sodium does not significantly affect the aPTT.
When used as curative treatment, aPTT can be prolonged by 1.5-2.2 times the control time at peak activity.
Pharmacokinetics: Absorption and Distribution: Maximum anti-Factor Xa and anti-thrombin (anti-Factor) activities occur 3 to 5 hours after SC injection of Enoxaparin. Mean peak anti-Factor Xa activity was 0.16 IU/mL (1.58 pg/mL) and 0.38 IU/mL (3.83 pg/mL) after the 20 mg and 40 mg clinically tested SC doses, respectively. Mean (n=46) peak anti-Factor Xa activity was 1.1 IU/mL at steady state in patients with unstable angina receiving 1 mg/kg SC every 12 hours for 14 days. Mean absolute bioavailability of Enoxaparin, after 1.5 mg/kg given SC, based on anti-Factor Xa activity is approximately 100% in healthy volunteers.
Enoxaparin pharmacokinetics appears to be linear over the recommended dosage ranges. After repeated subcutaneous administration of 40 mg once daily and 1.5 mg/kg once daily regimens in healthy volunteers, the steady-state is reached on day 2 with an average exposure ratio about 15% higher than after a single dose. Steady-state Enoxaparin activity levels are well predicted by single-dose pharmacokinetics. After repeated subcutaneous administration of the 1 mg/kg twice daily regimen, the steady state is reached from 4 with mean exposure about 65% higher than after a single dose and mean peak and trough levels of about 1.2 and 0.52 IU/mL, respectively. Based on Enoxaparin sodium pharmacokinetics, this difference in steady state is expected and within the therapeutic range.